volume 21, number 2, 2014 heart news views -...

1

http://ees.elsevier.com/jmcc/default.aspfor online submission

of manuscripts

Heart News

and views

Volume 21, Number 2, 2014

www.ishrworld.org

the news Bulletin of the International Society

for heart research

In this issue:

� Report on North American

Section Meeting . . . . . . . . . . . . . . 1

� President's Letter . . . . . . . . . . . . . 5

� Truth from Error

by Arnold M. Katz . . . . . . . . . . . . . 6

� ECI Activities . . . . . . . . . . . . . . . . . 8

� Report on ISHR-ES/SERVIER

Research Fellowship 2012 . . . . . .10

� 2013 Research Achievement

Award . . . . . . . . . . . . . . . . . . . . . . .13

� 2013 Distinguished Leader

Award . . . . . . . . . . . . . . . . . . . . . . . 14

� Meetings Calendar . . . . . . . . . . . 15

miami, fl

may, 2014

11111

report on the xxXV

north american section meeting:

novel strategies to combat heart failure

The 35th ISHR North American Section meeting was held in Miami, Florida thisyear, amidst the world’s most gorgeous beaches, beautiful sun-filled weather,and renowned South Beach night-life and culture. Of course, attendees were

most enthusiastic about the outstanding meeting program organized by Drs Josh Hareand Michael Kapiloff. The meeting was hosted by the Interdisciplinary Stem CellInstitute of the University of Miami Miller School of Medicine. The venue was the MiamiBeach Resort Hotel just north of South Beach, which provided attendees with ambiance,great food, and collaborative discussions throughout the meeting. Over 250 scientistsand physicians representing thirteen countries, from Japan to Canada, attended themeeting.

The meeting launched with a fabulous welcome reception for meeting Facultyon Sunday evening aboard the Venetian Lady yacht. Organizers Josh Hare and Michael

Dancing in the Starlight Ballroom at the meeting Banquet.

ECI activities in

Miami, fl

may, 2014

8

2

the news bulletin of the international society for heart research

Meeting organizers, Michael Kapiloff (left) and Joshua Hare welcome delegatesto the 2014 ISHR-NAS meeting in Miami Beach, FL.

Kapiloff welcomed everyone to the meetingand organized an amazing evening filledwith dining, music and entertainment. Awonderful time was had by all and theevening set a collegial tone of collaboration,networking and tantalizing scientificdiscussion.

The meeting schedule was packed withmorning and afternoon plenary sessions,posters, and networking lunches encom–passing the central theme of “NovelStrategies to Combat Heart Disease.” As aresult, the program encompassed a varietyof topics ranging from basic to clinicalresearch, stem cells to signal transduction.Participants in the sessions discussedextensively the contribution of aberrantcardiac signaling, ion channels andarrhythmias, stem cells and gene therapy,ischemia and cardioprotection, calciummicrodomains, contractile protein muta–tions, impaired metabolism and autophagy.Importantly, sessions gave vital insightsinto possible therapeutics, including thefuture of stem cell-, cellular- and ionotropic-based therapies. Excellent new approachesto enhancing our understanding of heartdisease were presented, which led to great

discussions and enthusiasm for thetreatment of heart disease among attend–ees. The presenters and attendees enjoyeddelicious hors d’oeuvres and beveragesand the atmosphere throughout themeeting was friendly and relaxed, providingthe opportunity for investigators to freelydiscuss their findings and possible futureresearch directions.

Plenary speakers kicked off the dailysessions with talks from Dr Andrew Schally,Nobel Prize winner in Medicine in 1977,“Hypothalamic Hormones: From Neuro–endocrinology to Therapy of Cancer andOther Diseases,” and Dr Pascal Gold–schmidt, Senior Vice President for MedicalAffairs and Dean of the University of MiamiMiller School of Medicine, “Of Aging,Inflammation, Frailty, and Stem Cells.” Talkswere consistent with this year’s mainthematic interest: conquering heart diseaseand finding new therapies for treatment.Some of the field’s most distinguishedscientists were formally recognized at themeeting and awarded for their extensivecontributions to science. First, DrEvangelia Kranias, the Hanna Professorand Director of Cardiovascular Biology

and Distinguished University Professorand Co-Director of the CardiovascularCenter of Excellence in the Department ofPharmacology and Cell Biophysics at theUniversity of Cincinnati College ofMedicine, was recognized as this year’sPeter Harris Research Achievement Awardrecipient. The Peter Harris ResearchAchievement Award recognizes a promi–nent investigator with a sustained anddistinguished record of major scientificachievement in the field of cardiovascularresearch, and whose research has had majorimpact on our understanding of treatmentof cardiovascular disease. Chaired by DrsMatt Hori and Elizabeth Murphy, DrKranias spoke on “Calcium Circuits in theHeart: A Matter of Life or Death,” whichfocused on the role of calcium cycling incardiac contractility and cell survival. DrKranias’ internationally recognized re–search program has provided fundamentalinsights into these regulatory mechanisms,particularly as they pertain to phos–pholamban and its regulation of calciumcycling through the sarcoplasmic reticulum.Indeed, she was the first to identify human

Meeting organizer, Dr Joshua Hare(Univ of Miami Miller School ofMedicine), with Nobel laureate,

Dr Andrew Schally (Veterans AffairsMedical Center)

3

volume 21, number 2, 2014

mutations in calcium cycling genes and toshow that these predispose individuals toarrhythmias and heart failure. Second, DrAsa Gustafsson, Associate Professor atthe Skaggs School of Pharmacy andPharmaceutical Sciences at the Universityof San Diego, was this year’s recipient ofthe Outstanding Investigator Award.Chaired by Drs Richard Moss and DavidEisner, Dr Gustafsson’s talk on the “Role ofMitochondrial Autophagy in Cardio–protection” focused on the contributionsshe has made in the areas of mitochondrialfunction and the molecular pathways thatregulate autophagy, particularly with regardto how BCL-2 proteins and the PINK1/Parkin pathway recognize and markdysfunctional mitochondria for degra–dation. Lastly, the meeting closed with thePresident’s Distinguished Lecture, givenby Dr Keiichi Fukuda, President of theISHR-Japanese Section and Professor andChief of the Department of RegenerativeMedicine and Advanced Cardiac Thera–peutics at Keio University School ofMedicine. Chaired by Dr Metin Avkiran,Dr Fukuda talked about “RegenerativeMedicine of the Heart using iPS cells,”which focused discussions on the field of

Drs David Eisner (Editor of the J MolCell Cardiol, left) and Richard Moss

(ISHR-Intl Secretary General) presentthe 2014 Outstanding Investigator

Award to Dr Asa Gustafsson (UCSD).

cardiac regeneration and the importance ofstem cells. Dr Fukuda was the first to reportthat bone marrow mesenchymal stem cellscould differentiate into cardiomyocytes invitro and that these cells could then betransplanted into the heart in vivo. He alsoreported that neural crest stem cells exist inthe heart and bone marrow and that theycould differentiate into multiple lineages,including cardiomyocytes. More recently,his work has focused on regeneration ofhuman cardiomyoctyes from stem cells forclinical use.

The meeting program not only includedexcellent presentations by accomplishedand well-established scientists, but alsopaid special tribute to the achievements ofyoung scientists. Indeed, the conferencewas well attended by graduate students,post-doctoral fellows and junior faculty.The early career symposium, consisting ofinvited talks by early investigators, an earlycareer discussion on alternative careerpaths, lunch with senior investigators, and

Drs Jeffrey Robbins (second from left), Chair of the Junior YIA competition,and Elizabeth Murphy (far right), President of ISHR-NAS, with (from left)Catherine Makarewich (winner), and finalists Sarah Schumacher-Bass,

Nirmala Hariharan and Maggie Lam.

an evening social, were lively and well-attended. In addition, one of the highlightsof the meeting was the Young Investigatorcompetitions. Annual Young InvestigatorAwards recognize outstanding research inthe field of cardiovascular research byjunior investigators. The applicants forthese awards fall into one of two categories:graduate students/early postdoctoralfellows and senior postdocs/early assistantprofessors. Two committees selectsfinalists to present their work at the meeting,where a panel of judges then make the finalaward based on the scientific merit of asubmitted unpublished manuscript, thequality of the oral presentation, and theresponses to questions asked during thediscussion. This year, the Junior YoungInvestigator Award was received byCatherine Makarewich, “Transient receptorpotential channels contribute to patho–logical structural and functional remodelingafter myocardial infarction,” mentored byDr Steve Houser. Finalists were NirmalaHariharan, “Nucleostemin antagonizes

4


senescence of cardiac progenitor cells,”mentored by Dr Mark Sussman; MaggieLam, “Protein kinetic signatures of theremodeling heart following isoproterenolstimulation,” mentored by Dr Peipei Ping;and Sarah Schumacher-Bass, “Paroxetine-mediated GRK2 inhibition reverses cardiacdysfunction and remodeling post-myo–cardial infarction,” mentored by Dr WallyKoch. The Senior Young InvestigatorAward was presented to Stephen Lange,“Defining the role of the stress sensorsMLP and CARP in signaling pathways thatlead to dilated cardiomyopathy,” mentoredby Dr Ju Chen. Finalists for this award werePaul Burridge, “Human induced pluripotentstem cells predicts breast cancer patient’spredilection to doxorubicin-inducedcardiotoxicity,” mentored by Dr JosephWu; Chad Grueter, “MED14 dependentsignaling from the heart enhances me–tabolism in adipose tissue and liver andconfers leanness,” mentored by Dr EricOlson; and Mark Kohr, “Glyceraldehyde-3phosphate dehydrogenase acts as a

Drs Yibin Wang (left), Chair of the Senior YIA competition, and Elizabeth Murphy(far right), President of ISHR-NAS, with (from left) Paul Burridge (finalist),

Stephen Lange (winner) and Chad Grueter (finalist).

Three Presidents and thePresident's Award:

Presidents Elizabeth Murphy (ISHR-NAS,left) and Metin Avkiran (ISHR-Intl, right)

present the 2014 President'sDistinguished Lecture Award to

Dr Keiichi Fukuda (President, ISHR-JPN).

mitochondrial trans-S-nitrosylase in theheart,” mentored by Dr Charles Steen–bergen. These talks were all exceptionaland thought-provoking; these talentedyoung investigators surely have incrediblybright futures ahead.

Other young investigators also hadopportunity to shine, presenting their workat one of two poster sessions, where a totalof 106 posters were presented. Posterpresentations were judged and threewinners were chosen and announced atthe meeting Banquet. The winners of theISHR International Poster Awards wereJonathan Hullman, “GRK5 ExacerbatesCardiac Pathology Through Activation ofthe NFAT Pathway,” mentored by Dr WallyKoch; Rushita Bagchi, “Scleraxis regulatescardiac extracellular matrix composition andfibroblast phenotype,” mentored by DrMichael Czubryt; and Christopher Murray,“State Dependent Photo-Crosslinking ofI

KS Using Unnatural Amino Acid Muta–

genesis,” mentored by Dr David Fedida.

Reviews of the meeting were very positiveand an abundance of praise was bestowed

upon the organizers. Indeed, Josh Hareand Michael Kapiloff put together awonderful program at a beautiful locationto make this year’s North American Sectionmeeting memorable. Next year’s annualmeeting will be organized by Chuck Murry,Michael Regnier, and Rong Tian and will beheld at the Grand Hyatt Hotel in Seattle,Washington on June 7-10th, 2015. Themeeting promises to be as informative,interesting and enjoyable as the one inMiami. I am looking forward to seeing youall there!

Maria Irene Kontaridis, Ph.D.Assistant Professor of MedicineHarvard Medical SchoolDepartment of CardiologyBeth Israel Deaconess MedicalCenter �

5

president 's letter

Miami Nice

Dear colleagues,

I write this letter on my return from the 35th Annual Meeting of the ISHR North AmericanSection in Miami Beach (May 12-15, 2014), which was organized under the theme “NovelStrategies to Combat Heart Failure”. From the outset, I wish to congratulate Joshua Hare andMichael Kapiloff, the local hosts of the meeting from the University of Miami, and the Sectionexecutive for putting together an outstanding programme. The breadth and quality of thescience was exceptional, comprising excellent lectures by invited faculty and cutting-edgeposter presentations selected from submitted abstracts, both complemented by lively (andmostly amicable!) debate.

What also impressed me enormously at the meeting was the range of initiatives undertaken by the North AmericanSection to embrace and nurture young investigators, and the enthusiasm and dedication of the young investigatorsthemselves. I was particularly struck by the statistic that around 120 emerging cardiovascular researchers participated in theEarly Career Investigator (ECI) events held on the first day, which were superbly organised by an ECI committee chaired bySarah Franklin (University of Utah). The Section recognised and rewarded the work of these investigators in multiple ways,including two Young Investigator Award competitions targeted at individuals at different stages of their evolving careers,a Poster Award competition (supported by ISHR International), and the inclusion of ECIs as invited speakers and co-chairsin the symposia. Notably, Litsa Kranias (University of Cincinnati), the dedicated Treasurer of the North American Section whoreceived the 2014 ISHR International Peter Harris Research Achievement Award at the meeting, chose to donate the honorariumassociated with that award to the Section, specifically to support ECI activities. This was a very meaningful gesture by Litsaand an exemplary illustration of the commitment of the Section leadership to supporting young investigators. The future ofcardiovascular science and indeed of the ISHR is reliant upon the success of the emerging researchers within our Sectionsand I applaud the North American Section for undertaking these ECI initiatives, whose value in sustaining the spirit and moraleof young investigators is undoubtedly even greater in the current funding environment. I am sure that other ISHR Sectionswill follow suit with comparable initiatives at their meetings later in the year, with the full endorsement of ISHR International.

The North American Section meeting was also the setting of a new venture by ISHR International, namely to hold itsannual Council meeting at ISHR Section meetings rather than at the Scientific Sessions of the American Heart Associationas in the past. The Council met in two sessions on Wednesday, May 14, where much discussion centred on how ISHRInternational may be able to provide further support to Section activities, to complement existing initiatives (e.g. sponsorshipof plenary Award lectures and ECI poster awards), as well as on preparations for our next World Congress in Buenos Aires,on April 18-21, 2016. I plan to give details of relevant new developments in my next letter, but suffice to say for now that theISHR International leadership is acutely aware of the financial challenges faced by our Sections in sustaining their annualscientific activities and is fully committed to helping them overcome these.

Another recent venture undertaken by the ISHR International leadership, in line with my objectives on taking office,is holding regular, web-based meetings of the Executive Committee in-between the annual Council meetings, to maintain greatercontiguity and liaison in managing the affairs of our Society. These present something of a logistical challenge for our trulyglobal Society, with the seven members of the Executive Committee located in five different time zones spanning from San Diego(UTC-7) to Osaka (UTC+9). Nevertheless, two such meetings have been held between the Council meetings in July 2013 (atthe San Diego World Congress) and May 2014 (at the North American Section meeting) and, looking forward, a timetable forvirtual meetings of the Executive Committee on a quarterly basis is being finalised through the good offices of the ISHRSecretary General, Richard Moss (University of Wisconsin). The occasional disruption to the regular sleep patterns of someparticipants in these meetings is unlikely to have a long-term cardiovascular impact, and is for a very good cause!

Until next time.

Metin Avkiran, PhD DScPresident, ISHR


6


Truth from Error:Sixty Years of Cardiology - 1952 to 2012

V: Positive Inotropic Therapy for Chronic Heart Failure

Arnold M. Katz, M.D.

In 1707, less than 80 years after Harveydescribed the circulation, Lancisipostulated that the “hidden oppression

and… heaviness of the precordium” inpatients with heart failure occurred when“weakened texture” reduced the ability ofa dilated left ventricle to eject blood (1).The ability of digitalis to reduce thesuffering of these patients, first describedby Withering in 1783 (2), suggested thatthe drug could alleviate this weakness. Forthe next two centuries physicians attributedthe benefits of cardiac glycosides to theirpositive inotropic effect, which was shownclearly in the late 19th century (3), alongwith their well-known ability to slow theheart in patients with atrial fibrillation (seebelow).

Evidence that cardiac contraction isweakened in patients with heart failure,which continued to accumulate throughoutthe 20th century, was confirmed by clar–ification of the concept of myocardialcontractility (4) and the experimentaldemonstration that contractility, which isreduced by overload-induced hypertrophy,decreases markedly when the heart fails(5).

In addition to cardiac glycosides, inotropicdrugs used 60 years ago included epi–nephrine and norepinephrine, which are β-adrenergic agonists now known to increasecyclic AMP synthesis, and caffeine, aphosphodiesterase (PDE) inhibitor thatdecreases cyclic AMP breakdown. Calciumsalts, strychnine and camphor had alsobeen used to strengthen the heart, but wereabandoned when it became clear that theirtoxicity far exceeds their efficacy.

Paired Pulse StimulationA report in 1963 that electrical stimulationof the heart in early diastole caused a markedincrease in contractility in the subsequentbeat (6) was greeted with great excitement(7). This powerful inotropic effect, whichhad been observed by Bowditch in 1871(8), suggested that heart failure could betreated by electrical stimulation of the failingventricle immediately after each spon–taneous beat, or by closely timed pairs ofstimuli. Called “paired pulse stimulation”(and sometimes “electrodigitalization”), thismethod was tried in only a handful ofpatients before it became apparent that itled to little or no clinical improvement andcould initiate dangerous arrhythmias.

“Powerful” Inotropic DrugsEfforts to increase contractility in failinghearts were again stimulated in 1978 whenacute administration of the bipyridinederivative amrinone was reported to causemarked hemodynamic improvement inpatients with severe heart failure (9).However an accompanying editorial noted

that positive inotropes could be deleteriousbecause increasing contractility alsoincreases cardiac energy demand (10). Thesubsequent finding that amrinone is a PDEinhibitor that increases calcium entry intocardiac myocytes raised the possibility thatthis class of drugs could initiate arrhythmias,exacerbate relaxation abnormalities andcause myocardial cell death (11). Theseand other concerns led Packer to observe“whenever we read initial enthusiasticreports of a new ‘breakthrough’ [thebenefits] are commonly expressed withgreat passion and enthusiasm, and thisenthusiasm is almost always subsequentlytempered by reports of drug failure oradverse reactions” (12).

These different views led to a fiercecontroversy regarding the safety ofinotropic drugs, especially those whoseeffects are mediated by cyclic AMP. Thelethal effects of β-adrenergic agonists inchronic heart failure were quickly doc–umented (13), but a number of small trialssuggested that PDE inhibitors could relievesymptoms in these patients without causingadverse effects. As this question had notbeen examined in controlled trials designedto identify a significant effect on survival,Packer and Leier (14) compared mortalityin several small studies of PDE inhibitorand vasodilator treatment of heart failure.This showed one year mortality to be 45%in patients taking vasodilators and 74% inthose treated with inotropic drugs. Thecontroversy continued until 1991 when thefirst large placebo-controlled trial of a PDEinhibitor (milrinone) was stopped pre–maturely because of excess mortality inpatients receiving the drug (15). Asubsequent analysis of trials using PDE

7

inhibitors in patients with chronic heartfailure confirmed that this class of inotropescauses a significant (17%) reduction insurvival (16).

DigitalisAs already noted, clinical observationsmade it clear that digitalis can providedramatic symptomatic relief in patients withheart failure. Until the 1950s, however, themost common cause of this syndrome wasrheumatic valvular disease (17), whichoften leads to atrial fibrillation. This raisedthe possibility that the benefits of cardiacglycosides were due mainly to their abilityto slow the rapid ventricular rate caused bythis arrhythmia rather than their inotropiceffect. By increasing the likelihood thattoday’s heart failure patient will be in sinusrhythm, the decreased prevalence of atrialfibrillation reduced the potential benefitsof cardiac glycosides. Along with thedemonstration that other less toxic drugsimprove symptoms and prolong survival inheart failure, this change led many toquestion the value of digitalis for treatingthis syndrome as it presents today.

In 1990 a meta-analysis of trials thatincluded 645 heart failure patients whowere in sinus rhythm found a 72% greaterbenefit from treatment with cardiacglycosides than placebo (18); however,the key measurement in this study wasclinical deterioration and not mortality. Adifferent conclusion was reached 7 yearslater when a large (3397 patients) randomizedplacebo-controlled trial showed thatdigoxin had no effect on survival (19).Although fewer patients randomized todigoxin died from worsening heart failure,there were more deaths in this group fromarrhythmias, coronary disease and othercardiac causes. This failure of digoxin toimprove survival in heart failure patientswho were in sinus rhythm discouraged theclinical use of the cardiac glycosides.

The finding that the inotropic effect ofcardiac glycosides did not improve survival

in heart failure supported the view that themajor problem in this syndrome is notdecreased contractility, but instead isprogressive deterioration of the failing heart(20). This issue is discussed in the nextarticle in this series, which describes theresponses to β-adrenergic blocking drugs.

References1. Jarcho S. The Concept of Heart Failure.

From Avicenna to Albertini. CambridgeMA, Harvard University Press. 1980, p266.

2. Withering W. An Account of the Foxgloveand Some of its Medical Uses.Birmingham, Swinney, 1785.

3. Fothergill JM, The Hastings Prize Essay,1870. On digitalis: Its mode of action andits use. Br Med J 1871; i: 27-29.

4. Sarnoff SJ. Myocardial contractility asdescribed by ventricular function curves:observations on Starling’s Law of theHeart. Physiol Rev 1955; 35: 107–122.

5. Spann JF Jr., Buccino RA, SonnenblickEH, Braunwald E. Contractile state ofcardiac muscle obtained from cats withexperimentally produced ventricularhypertrophy and heart failure. Circ Res1967; 21: 341-354.

6. Lopez JF, Edelist A, Katz LN. Slowing ofthe heart rate by artificial electricalstimulation with pulses of long durationin the dog. (Abstr) Circulation 1963; 28;759.

7. Cranefield PF (Ed). Conference on PairedPulse Stimulation in the Heart. Bull NYAcad Med 1965; 41: 417-570, 575-747.

8. Bowditch HP. Über dieEigenthümlichkeiten der Reizbarkeit,welche die Musklefasern des Herzenszeigen. Ber sächs Ges (Akad) der Wiss1871; 23: 652-689.

9. Benotti JR, Grossman W, Braunwald E,Davolos DD, Alousi AA. Hemodynamicassessment of amrinone. A new inotropicagent. N Engl J Med 1978; 299: 1373-1377.

10. Katz AM. A new inotropic drug: Itspromise and a caution. N Engl J Med1978; 299: 1409-1410.

11. Katz AM. Potential deleterious effects ofinotropic agents in the therapy of heartfailure. Circulation 1986; 73 (Suppl III):184-190.

12. Packer M. Vasodilator and inotropictherapy for severe chronic heart failure:Passion and skepticism. JACC 1983; 2:841-852.

13. Yusef S, Teo K. Inotropic agentsincrease mortality in patients withcongestive heart failure. (Abstr)Circulation 1990; 82 (Suppl III): III-673.

14. Packer M, Leier CV. Survival incongestive heart failure during treatmentwith drugs with positive inotropicactions. Circulation 1987; 75 (SupplIV); IV-55 - IV-63.

15. Packer M, Carver JR, Rodeheffer RJ,Ivanhoe RJ, DiBianco R, Zeldis SM,Hendrix GH, Bommer WJ, Elkayam U,Kukin ML, et al. Effect of oralmilrinone on mortality in severe chronicheart failure. The PROMISE StudyResearch Group. N Engl J Med 1991;325: 1468-1475.

16. Amsallem E, Kasparian C, Haddour G,Boissel J-P, Nony P. PhosphodiesteraseIII inhibitors for heart failure. CochraneDatabase Syst Rev. 2005: CD002230.

17. Wilson MG. Rheumatic Fever. NewYork, The Commonwealth Fund, 1940.

18. Jaeschke R, Oxman AD, Guyatt GH.To what extent do congestive heartfailure patients in sinus rhythm benefitfrom digoxin therapy? A systematicoverview and meta-analysis. Am JMed.1990; 88: 279-286.

19. The Digitalis Investigation Group. Theeffect of digoxin on mortality andmorbidity in patients with heart failure.N Engl J Med 1997; 336: 525-533.

20. Katz AM. Cardiomyopathy ofoverload. A major determinant ofprognosis in congestive heart failure. NEngl J Med 1990; 322: 100-110.

Arnold M. Katz, M.D.Professor of Medicine Emeritus,

Univ. of Connecticut School of Medicine,

Honorary Professor of Med. and Physiol.,

Geisel Medical School at Dartmouth

[email protected] �

Volume 21, Number 2, 2014

8

ISHR-North American SectionMeeting, Miami, FL, May 12-15,2014

The International Society for HeartResearch is dedicated to promoting

and supporting its young investigators,who represent the future of cardiovascularresearch and this society. The ISHR-NASEarly Career Investigator (NAS-ECI)committee, chaired by Dr Sarah Franklin(Univ of Utah; 2012 Senior ISHR-NAS YIAwinner), organized an extremely successfulseries of events at this year’s Sectionmeeting designed by and for young ISHRinvestigators. More than half the meetingdelegates signed up to participate in one ormore of the following events:

ECI Symposium (May 12, 9:00 – 10:30 am):Abstracts submitted by ECIs were eval–uated by the NAS-ECI committee, and 9abstracts were chosen for presentation inthis symposium chaired by Randi Parksand Samarjit Das.

Alternate Career Paths Workshop (May12, 10:45-11:45 am): Panelists included Dr

Lisa Schwartz-Longacre, Program Officerat NHLBI/NIH, Wayne Bowden, LeadProgram Manager at BioRASI, and Dr GrantBudas, Scientist at Gilead Sciences. Briefpresentations by each panelist werefollowed by a question and answer period.The workshop was chaired by Drs MarkKohr and Sakthivel Sadayappan.

ECI Lunch with Senior Investigators (May12, 12:00-1:00 pm): ECIs gathered aroundthe table with invited senior cardiovascularresearchers for an informal lunch dis–cussion. More than 60 ECIs and 20 seniorinvestigators participated in this popularevent.

ECI Social (May 13, 7:00-10:00 pm): Anunexpected downpour did not dampen thespirits of participants in this socialnetworking event! Drinks and finger foodaccompanied the meet and greet.

In addition to these ECI-organized events,the meeting included several other oppor–tunities to showcase ISHR-NAS’s younginvestigators:

NAS-ECIs were invited by meetingorganizers to co-chair the majority of themeeting symposia along with a seniorinvestigator. This opportunity providedinvaluable experience and visibility foryoung investigators.

ISHR-NAS sponsors an annual YoungInvestigator Competition, in whichcandidates in each of two experiencecategories (Junior (graduate students, earlypostdoctoral fellows) and Senior (latepostdoctoral fellows, early AssistantProfessors) submit an application thatconsists of an unpublished manuscript,CV and recommendation letter. FourFinalists in each category were chosen bycommittees of senior investigators (chaired

ISHR-north american section early

career investigator events

Early career investigators listen attentively to talks presented by their peersat the ECI Symposium.

ECI Committee member, Samarjit Das(JHMI), presents his poster to

Prague delegate, Anna Chytilova(Institute of Physiology ASCR).


9

by Drs Howard Rockman (Senior) andJeffrey Robbins (Junior)) to give a brief oralpresentation of their work followed byquestions from the judges. This year’swinners were Stephan Lange (Senior) andCatherine Makarewich (Junior). The SeniorYIA winner becomes a member of the ISHR-NAS Council (2-year term), co-chair of theISHR-NAS ECI committee for one year (July,2014 to June, 2015), and chair of thecommittee the following year.

ISHR-Intl sponsors the ISHR-Inter–national Poster Competition at the WorldCongress and each ISHR Section meetingthat chooses to participate. The awardsrecognize outstanding young investi–gators whose posters demonstrate bothexcellence in research and clarity ofpresentation. Posters were evaluated by asmall panel of senior investigators, co-chaired by Drs Federica del Monte andMark Sussman (representatives of theISHR-Intl Council). This year’s winnerswere Rushita Bagchi, Jonathan Hullmanand Christopher Murray.

More ECI events are being planned by theNAS-ECI committee led by incoming

ISHR-Intl Council members and poster competition organizers, Federica del Monte(left) and Mark Sussman (right) with ISHR-Intl Poster Award Winners (from left)

Chris Murray (Univ of British Columbia), Rushita Bagchi (Univ of Manitoba)and Jonathan Hullman (Thomas Jefferson Univ).

ECIs gather around the table for an informal lunch with senior investigatorsin the Starlight Ballroom.

chairman, Dr Chen Gao (UCLA, winner ofthe 2013 ISHR Richard J Bing Award forYoung Investigators) for the 2015 ISHR-NAS Section meeting in Seattle, WA.Make plans now to attend! In the meantime,network with your fellow ISHR-NAS ECIson Facebook and LinkedIn. �

2014 NAS-ECI Committee:Sarah Franklin (Chair)Chen Gao (Co-chair)Grant BudasSamarjit DasJeffrey EricksonAlice HoMark KohrChris MurryRandi ParksMaggie LamCatherine PassarielloSakthivel Sadayappan

Faculty Advisors:Chris BainesLitsa KraniasJeffrey RobbinsElizabeth Murphy, President ISHR-NAS


10


mitochondrial s-nitrosation and

cardioprotection by mitosno:

a novel mitochondria-targeted

s-nitrosothiol

In May 2012 I had the great honour to receive the ISHR-ES/SERVIER ResearchFellowship at the meeting of the ISHR European Section in Belgrade. Every year

a basic scientist gets awarded with this prestigious fellowship to support researchin the cardiovascular field. During my fellowship I worked as a postdoctoralresearcher in the Department of Medicine at the University of Cambridge under thementorship of Dr Thomas Krieg and Dr Michael Murphy. My research project involvedinvestigating protective mechanisms against myocardial ischaemia reperfusioninjury (IRI) with a focus on S-nitrosation of mitochondrial proteins by a novel S-nitrosating agent, MitoSNO. It is a privilege to present the results of my fellowshipresearch project.

Timely reperfusion of acute ischaemicmyocardium is essential for myocardialsalvage but also results in a unique form ofmyocardial damage. Over the last twodecades, it has become increasingly clearthat reactive oxygen species (ROS)production is greatly increased in the post-ischaemic heart and serves as a criticalcentral mechanism of post-ischaemic injury.The mechanism behind the ROS increaseand how it can be prevented are unknown.Nitric oxide (NO) has been shown to beprotective against IRI in the heart1 andNO’s ability to S-nitrosate cysteine residuesis correlated with protection2. In order totest the mechanism involved in cardio–protection by S-nitrosation we determinedthe ability of a novel mitochondria-targetedS-nitrothiol to protect against cardiacdamage. The lipophilic triphenylphos–phonium (TPP) cation can be used toselectively target mitochondria rapidly invivo and deliver compounds to themitochondrial matrix at very high concen–trations, effectively protecting the mito–chondria from oxidative damage3. Recently,the mitochondria-targeted S-nitrosothiol(MitoSNO) has been developed byattaching an SNO moiety to TPP (Fig 1A) 4.MitoSNO selectively accumulates several-hundred fold in mitochondria thereby

Figure 1A MitoSNO accumulates several hundred-fold within mitochondria

and thereby S-nitrosates mitochondrial proteins;in contrast, the untargeted NO-donor SNAP modifies non-mitochondrial proteins.

B Application of MitoSNO at reperfusion reduced infarct sizein an acute myocardial infarction model in mice.

The targeted control compound MitoNAP and SNAP had no effect on infarct size.

selectively S-nitrosating mitochondrialproteins and protecting mitochondria fromIRI2,5.

In order to test MitoSNO’s cardioprotectiveeffect, mice were subjected to 30 min regionalischaemia followed by 2 h reperfusion.

Carmen Methner, PhD

Application of MitoSNO at reperfusionled to a profound infarct size reduction(Fig 1B). Neither the untargeted NO donorSNAP, nor MitoNAP, the mitochondria-targeting moiety alone, was effective whenapplied at the same concentration asMitoSNO. We next sought to identify the

11


S-nitrosated targets, which mediated thecardioprotection seen with MitoSNOtreatment. Tail vein injection of MitoSNOjust prior to reperfusion lead to selective S-nitrosation of mitochondrial proteins in theheart while SNAP only modifies non-mitochondrial proteins in the cytoplasmand blood plasma. In particular, S-nitrosated proteins of respiratory complexI seem to be relevant in vivo. Complex Iactivity was found decreased at onset ofreperfusion in MitoSNO-treated micecompared to untreated mice and returnedto initial values after 30 min reperfusion,indicating that inhibition of complex Iactivity by S-nitrosation is reversible.

Finally, we identified the ND3 subunit ofcomplex I as being the critical proteinmodified by MitoSNO-mediated S-nitros–ation with a half life of about 5 min6.Interestingly, the ND3 S-nitrosation onlyoccurred after the cysteine was exposedthrough an ischaemia-induced confor–mational change of complex I.

In the next step we tested whether there isa causal relationship between the Mito–SNO-induced ND3 S-nitrosation and theproduction of damaging ROS. Mito–chondrial ROS production occurs pre–dominantly at complex I and this productionseems to be a major contributor to re–perfusion injury, as well as the redoxsignalling responsible for remodelling andchronic heart failure development7. In orderto test mitochondrial ROS production invivo, we used the recently developed massspectrometric probe, MitoB, which reflectsmitochondrial ROS production via itsconversion by hydrogen peroxide to MitoPselectively within mitochondria. We couldshow that IRI increased the MitoP/MitoBratio, indicating an increase in mitochondrialROS6. MitoSNO treatment abolished thisincrease. Furthermore, MitoSNO decreasedmitochondrial oxidative damage, as deter–mined by measuring the oxidative damagemarker protein carbonyls, as well asapoptosis6.

Figure 2Proposed model by which S-nitrosation of ND3 Cys 39 protects

against ischaemia reperfusion injury.

In summary, we propose the mechanismdrawn in Figure 2 by which S-nitrosationof complex I ND3 Cys39 protects againstmyocardial IRI. The crucial cysteine isoccluded during normal complex I activity,but during ischaemia this cysteine becomesexposed due to low complex I activity.Reperfusion of the ischaemic tissue causesrapid reactivation of complex I and therebyproduction of hydrogen peroxide, which inturn causes oxidative damage and cell deathunderlying IRI. When MitoSNO is presentduring reperfusion, the exposed ND3 Cys39becomes S-nitrosated and complex I lockedin a low activity state, decreasing ROSproduction upon reperfusion. Subse–quently reduction of S-nitrosothiol byglutathione gradually reactivate complex I.

While we could show that MitoSNOselectively S-nitrosated mitochondrialproteins and had profound infarct reducingproperties in the acute phase, it was notclear whether this mechanism could prevent

long-term changes post-MI.

In the next set of experiments mice weresubjected to 30 min left coronary arteryocclusion followed by a prolongedreperfusion period of 28 days. One dayafter surgery late-gadolinium enhancedmagnetic resonance imaging (MRI) wasperformed which confirmed the previoushistopathological findings of marked infarctsize reduction in the MitoSNO-treated mice.Furthermore, increased LV function wasobserved7. After 28 days this protectiveeffect was still present and we saw preservedcardiac function and decreased tissuefibrosis in MitoSNO-treated animalscompared to controls (Fig 3). Since therelease of free NO is known to cause changesin blood pressure and haemodynamics thatcan limit use in patients, we also testedMitoSNO’s effect on blood pressure andhaemodynamics and found that MitoSNOdid not alter any of those parameters7.

12


Taken together, we could show that (1)mitochondrial protein S-nitrosation iscardioprotective, (2) Complex I ND3 Cys39S-nitrosation is crucial in the protectivemechanism of MitoSNO, (3) MitoSNO,when applied acutely post-MI protectsagainst acute and long-term injury. Withthese data we demonstrate the cardio–protective properties of MitoSNO againstischaemia reperfusion injury in the heart aswell as the underlying mechanism. There–fore MitoSNO is a potential treatmentcandidate for patients with acute myo–cardial infarction.

References

1. Cohen MV, Yang XM, Liu YP,Solenkova NV and Downey JM.Cardioprotective PKG-independent NOsignaling at reperfusion. Am J PhysiolHeart Circ Physiol 2010; 299: 2028–36.

2. Prime TA, Blaikie FH, Evans C,Nadtochiy SM, James AM, Dahm CC etal. A mitochondria-targetedS-nitrosothiol modulates respiration,nitrosates thiols, and protects againstischemia-reperfusion injury. Proc NatlAcad Sci USA 2009; 106: 10764–9.

3. Ross MF, Kelso GF, Blaikie FH, JamesAM, Cochemé HM, Filipovska A et al.Lipophilic triphenylphosphoniumcations as tools in mitochondrialbioenergetics and free radical biology.Biochem (Mosc) 2005; 70: 222–30.

4. Porteous CM, Logan A, Evans C,Ledgerwood EC, Menon DK, AigbirhioF et al. Rapid uptake of lipophilictriphenylphosphonium cations bymitochondria in vivo followingintravenous injection: implications formitochondria-specific therapies andprobes. Biochim Biophys Acta 2010;1800: 1009–17

Figure 3Cardiac function is improved 28 days post infarction in MitoSNO-treated mice (A).

Representative images of Masson Trichrome stainingof control and MitoSNO-treated hearts (B)

and quantification of collagen content in those slides (C).

5. Chouchani ET, Hurd TR, NadtochiySM, Brookes PS, Fearnley IM, LilleyKS et al. Identification of S-nitrosatedmitochondrial proteins by S-nitrosothioldifference in gel electrophoresis (SNO-DIGE): implications for the regulation ofmitochondrial function by reversible S-nitrosation. Biochem J 2010; 430: 49–59.

6. Chouchani ET, Methner C, NadtochiySM, Logan A, Pell VR, Ding S et al.Cardioprotection by S-nitrosation of acysteine switch on mitochondrialcomplex I. Nat Med 2013; 19.

7. Methner C, Chouchani ET, BuonincontriG, Pell VR, Sawiak SJ, Murphy MP andKrieg T. Mitochondria selective S-nitrosation( by mitochondria-targeted S-nitrosothiol protects against post-infarctheart failure in mouse hearts. Eur J HeartFailure 2014 (in press).

Carmen Methner, PhD �

Carmen Methner PhD was the winnerof the ISHR-ES/SERVIER ResearchFellowship 2012 at the XXXI EuropeanSection Meeting (Belgrade, Serbia:May 2012).

13


Eric Olson is professor and chair ofthe Dept of Molecular Biology atthe University of Texas South–

western Medical Center in Dallas, where healso holds the Robert A. Welch Distin–guished Chair in Science, the PogueDistinguished Chair in Research on CardiacBirth Defects, and the Annie and WillieNelson Professorship in Stem Cell Re–search. Dr Olson attended Wake Forest University,receiving a B.A. in Chemistry and Biologyand a Ph.D. in Biochemistry. He later alsoreceived an honorary doctorate from hisalma mater. After postdoctoral training atWashington University School of Medi–cine, Dr Olson assumed his first facultyposition at MD Anderson Cancer Center in1984, where he became Professor and Chairof Biochemistry and Molecular Biology in1991. In 1995, he founded the Departmentof Molecular Biology at UT Southwestern. Dr Olson was an early pioneer in thediscovery of the major cardiac transcriptionfactors and showed how these factorsfunction within an evolutionarily con–served gene regulatory network toorchestrate heart formation in organismsranging from fruit flies to mammals. DrOlson discovered the MEF2 transcriptionfactor, which activates the genes requiredfor sarcomere formation and cardiaccontractility. He and his colleaguesdiscovered the first chamber-restrictedcardiac transcription factors, Hand1 andHand2, and demonstrated that they controlgrowth of the left and right ventricles,respectively, and recently showed that four

cardiac transcription factors (Gata4, Hand2,Mef2C and Tbx5) can reprogram cardiacfibroblasts into beating cardiomyocyteswithin the intact heart following myocardialinfarction, diminishing scar formation andenhancing cardiac function. Thesefindings offer a promising new strategy forheart repair, bypassing many of theobstacles associated with other ap–proaches. Dr Olson discovered the myocardin familyof transcriptional coactivators, whichfunction as master regulators of cardio–vascular gene expression. Other importantcardiac transcription factors discoveredby Dr Olson include, the homeodomain-only protein (HOP), which regulatescardiomyocyte cell number during devel–opment; the HRT family of transcriptionfactors, which mediate Notch signaling inearly heart formation; and CAMTA, whichfunctions as a calcium-dependent regulatorof heart growth. In recent studies, Dr Olson and colleaguesfound that the hearts of neonatal mice canfully regenerate after partial surgicalresection, but this capacity is lost early inlife due to irreversible suppression ofcardiomyocyte proliferation. Thesefindings demonstrate a previously un–recognized regenerative capacity of themammalian heart and have provided apowerful new model for uncovering themolecular basis of heart regeneration. In earlier studies, Dr Olson was the first torecognize the importance of the calcium-dependent protein, calcineurin, in cardiac

hypertrophy and failure, opening a newdirection for the field of molecular car–diology. He also showed calcium-dependent protein kinases control themolecular interaction between MEF2 andclass II histone deacetylases (HDACs),providing a trigger for stress-dependentremodeling of the heart. Olson’s discoverythat HDACs function as key regulators ofcardiac gene expression led to the ad–vancement of HDAC and HDAC kinaseinhibitors as new classes of cardio-protective drugs, currently in clinicaldevelopment. Most recently, Dr Olson discoveredsignature patterns of microRNAs associ–ated with cardiovascular development anddisease and showed how microRNAsregulate numerous facets of cardiovascularbiology, including myocyte growth andsurvival, contractility, energy metabolism,fibrosis, and angiogenesis. He discoveredthat myosin heavy chain genes encodemicroRNAs in their introns and that thesemicroRNAs control cardiac gene expressionand contractility. Thus, myosin genes notonly encode the major contractile proteinsof muscle but act more broadly to controlthe gene expression programs and func–

eric olson, ph.d.

2013 recipient of the ishr

research achievement award

(2013; san diego, ca)

(continued on page 15)

14


Dr Mattiazzi is Consultant Professorof Physiology and Biophysics atthe Faculty of Medicine of the

University of La Plata and SuperiorInvestigator of the National ResearchCouncil of Argentina (CONICET). Previ–ously she was professor and chairman ofthe Department of Physiology and Bio–physics at the Faculty of Medicine of LaPlata University and Director of theCardiovascular Research Center in La Plata,Argentina. After retiring from thesepositions, she continues to perform activeresearch at the Cardiovascular ResearchCenter and postgraduate teaching activities.She was the founder and is the presentDirector of the Magister of BiomedicalResearch at the Faculty of Medicine,University of La Plata.

Dr Alicia Mattiazzi is not only regarded asan outstanding leader of South Americancardiovascular research but is also widelyrecognised by her peers for her continuousefforts to promote cardiovascular andphysiological research throughout the LatinAmerican Scientific community. She hasbeen an active member of the ISHR,contributing to most of the ISHR WorldCongresses and, in 2001, serving on thescientific program committee of the XVIIWorld Congress of the ISHR in Winnipeg,Canada .

Closer to home, Dr Mattiazzi served theLatin American Section of the ISHR(LAISHR) for many years, acting in differentpositions, including President and Past-President. During this time, she worked topromote the ISHR bylaws throughout Latin

America and to attract new members. DrMattiazzi organized five annual LAISHRmeetings, including a satellite meeting tothe XVIII ISHR World Congress inBrisbane, Australia (2004). She was deeplyinvolved in the other four meetings as amember of the organizing or scientificprogram committee. In all these meetings,Dr Mattiazzi has upheld the higheststandards, putting together solid scientificprograms and encouraging the partici–pation of young investigators andstudents. These meetings set a newstandard for scientific reporting ofcardiovascular research in Latin Americaand through them, Dr Mattiazzi success–fully promoted the integration of heartresearch groups within Latin America andaround the world.

Dr Mattiazzi worked most of the time in LaPlata, but spent extensive periods of timeworking in different outstanding labo–ratories outside Argentina, mainly inSweden and the USA. She published morethan 100 papers in high profile journalsthroughout her career and her main researchinterests have been cardiac mechanics andthe regulation of cardiac contractility andrelaxation induced by physiological,pathophysiological and pharmacologicalinterventions in intact myocardial prepa–rations and isolated cells, includingstimulation frequency, α and β adrenergicagents, Angiotensin II, acidosis, andischemia-reperfusion injury.

A major contribution of Dr Mattiazzi andher colleagues was to demonstrate therelevance of the phosphorylation of theThr17 residue of phospholamban (PLN), theCa2+-calmodulin-dependent protein kinaseII (CaMKII) site, in the modulation ofmyocardial relaxation and contractilityunder β-adrenoceptor stimulation. Theseresults were described in a series of papers,the first of which appeared in the early1990s (Vittone et al., Am J Physiol, 1990).By the use of phosphorylation site-specificantibodies combined with the quantificationof 32P incorporation into PLN and thesimultaneous measurement of mechanicalactivity, she and her group furtherdemonstrated that cAMP (Ser16)- and Ca2+-calmodulin (Thr17)-dependent pathways ofPLN phosphorylation can occur indepen–dently of each other in the intact heart. Themost representative of this series of paperswere those published in J Biol Chem,(Mundiña-Weilenmann et al., 1996, Vittoneet al., 1998).

In subsequent work, she envisaged therole of CaMKII-dependent phosphory–lations in different pathophysiologicalconditions, including ischemia/reper–fusion, acidosis and arrhythmias. In a seriesof publications, she demonstrated the dualeffect of CaMKII-dependent phosphory–lations (beneficial or detrimental), in thereversible and irreversible ischemia/reperfusion injury, respectively (Forexample, Said et al., Am J Physiol, 2003), as

dr alicia Mattiazzi

2013 recipient of the ishr

distinguished leader award

(2013; San Diego, ca)

15

ISHR MEETINGS CALENDAR


well as the necessary and determinant roleplayed by the phosphorylation of Thr17 ofPLN in the contractile and intracellular Ca2+

recovery of the stunned heart (Valverde etal., Cardiovasc Res, 2006). She also showedthe importance of CaMKII-dependentphosphorylations at the sarcoplasmicreticulum level, as main players in thecascade of events that leads to apoptosisand necrosis in ischemia/reperfusion (Vila-Petroff et al., Cardiovasc Res, 2007; Salaset al., J Mol Cell Cardiol, 2010) and inacidosis, ischemia/reperfusion and digi–talis-induced arrhythmias (Said et al., Am J

Physiol, 2008, and J Mol Cell Cardiol,2011, Gonano et al., Circulation: Ar–rhythmias and Electrophysiology, 2011).Dr Mattiazzi and her colleagues alsoshowed for the first time, how oxidativestress resets the Ca2+-dependence ofCaMKII to extremely low (sub-physi–ological) Ca2+ levels, to promote myocytedeath across different species (Palomequeet al., Circ Res, 2009). This novel andpreviously unrecognized mode of CaMKIIactivation constitutes a new paradigm inthe intracellular signalling pathwaysmediated by CaMKII which may be relevant

to a large number of diseases in whichreactive oxygen species are increased.

Based on her accomplishments, DrMattiazzi has been invited to givenumerous national and internationallectures and seminars. She is a fellow of theAHA and the ISHR and has receivednumerous awards, among which are theGuggenheim Fellowship, the BernardoHoussay Award for outstanding scientificcareer and the International WomenAssociation Award. �

tions of striated muscles through theexpression of a family of intronic micro–RNAs. The dual functions of myosin genes,encoding both protein and microRNA,serve as a paradigm for the integration ofmicroRNAs with complex cellular pro–cesses. In the course of these studies, DrOlson uncovered a central role for the heartin the control of systemic energy homeo–stasis and metabolism via a microRNAregulatory circuit, providing a new entrypoint into the pathways of obesity andmetabolic syndrome. The many genes and regulatory mech–anisms discovered by Dr Olson haveestablished new principles of gene

regulation and have provided noveltherapeutic targets for normalizing cardiacfunction in the settings of congenital andacquired heart disease. Toward that end,Dr Olson has cofounded several bio–technology companies to advance studiesfrom his lab toward clinical applications. Dr Olson is a member of the AmericanAcademy of Arts and Sciences, the U.S.National Academy of Sciences, and theInstitute of Medicine. His awards includethe Pasarow Award in CardiovascularMedicine, the Pollin Prize in PediatricResearch, and the Passano Prize. In 2009,the French Academy of Science awardedDr Olson the Fondation Lefoulon-Dela–

lande Grand Prize for Science. He is also arecipient of the Basic Research Prize, theResearch Achievement Award and theInaugural Distinguished Scientist Awardfrom the American Heart Association. In2013, Dr Olson received the March of DimesPrize in Developmental Biology. Dr Olson has trained successive gener–ations of students and postdoctoralfellows, many of whom are emerging asleaders in cardiovascular medicine. In hisspare time, Dr Olson plays guitar andharmonica with the Transactivators, a rock‘n’ roll band inspired by the Texas icon,Willie Nelson, who established theProfessorship that Olson holds. �

(continued from page 13)

� November 28-29, 2014. XXXI Annual Meeting of the Japanese Section. Nagoya, Japan. Inquiries: Toyoaki Murohara,

[email protected]

� June 7-10, 2015. XXXV Annual Meeting of the North American Section. Seattle, WA. Inquiries: Charles Murry,

[email protected]

� July 2-5, 2015. XXXIII Annual Meeting of the European Section. Bordeaux, France. Inquiries: Pierre Dos Santos,

[email protected]

� August, 2015. XXXVIII Annual Meeting of the Australasian Section. Melbourne, Australia.

� April 18-21, 2016. XXII World Congress of the ISHR. Buenos Aires, Argentina.

16

HEART NEWS AND VIEWS

is the official News Bulletin of theInternational Society for HeartResearch and is published everyfourth month.

EditorL. Anderson LobaughDurham, NC, USAE-mail [email protected]

Founding EditorT.J.C. RuigrokWijk bij Duurstede, The NetherlandsE-mail [email protected]

Editorial BoardR.A. AltschuldColumbus, OH, USAM. AvkiranLondon, UKPresidentR. BolliLouisville, KY, USAT. IzumiKanagawa, JapanJapanese SectionB. BernardoMelbourne, AustraliaAustralasian SectionX.Y. LiBeijing, ChinaChinese SectionA. MattiazziLa Plata, ArgentinaLatin American SectionB. McDermottBelfast, UKEuropean SectionE. MurphyBethesda, MD, USAPresident-ElectT. RavingerovaBratislava, Slovak RepublicA.-M.L. SeymourHull, UKN. TakedaTokyo, JapanK.K. TalwarChandigarh, IndiaIndian SectionD. EisnerManchester, UKEditor-in-Chief, JMCCB.J. WardLondon, UKK.T. WeberMemphis, TN, USA

Editorial Office3711 Lochn'ora ParkwayDurham, NC 27705USA.Phone/Fax: +1 919 493 4418


volume 21, number 2, 2014 heart news views -...

Documents