editorial oxidized ldl in inflammation: from bench to...

Hindawi Publishing CorporationMediators of InflammationVolume 2013, Article ID 762759, 3 pageshttp://dx.doi.org/10.1155/2013/762759

EditorialOxidized LDL in Inflammation: From Bench to Bedside

Ishak Ozel Tekin,1 AsJm Orem,2 and Ronit Shiri-Sverdlov3

1 Department of Immunology, Bulent Ecevit University, School of Medicine, 67600 Zonguldak, Turkey2Department of Biochemistry and Clinical Biochemistry, Karadeniz Technical University, School of Medicine, 61080 Trabzon, Turkey3 Department of Molecular Genetics, Maastricht University (MUMC), Universiteitssingel 50, 6229 ER, Maastricht, The Netherlands

Correspondence should be addressed to Ishak Ozel Tekin; [email protected]

Received 28 October 2013; Accepted 28 October 2013

Copyright © 2013 Ishak Ozel Tekin et al. This is an open access article distributed under the Creative Commons AttributionLicense, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properlycited.

Oxidation of LDL is considered a marker of inflammation.Indeed, numerous studies have documented that oxidizedlipids as well as products derived from their decompositionhave deleterious biological properties. As such a betterunderstanding of the underlying pathological mechanismsis necessary for the development of novel therapeutic agentsand diagnostic tools. Multiple experimental data carried outin cellular lines and animal models of atherosclerosis supportthe proatherogenic role of oxidized LDLs through severalmechanisms which include chemotactic and proliferatingactions on macrophages, stimulation of smooth muscle cells,and eliciting apoptosis. While the role of oxLDL in relationto atherosclerosis has been investigated thoroughly, its rolein other inflammatory diseases is recently emerging as well.

In this special issue, we report how findings regardingoxLDL in inflammation at the benchside can be translatedto the bedside and how these observations may help clinicalpractice. The papers have been contributed by a number ofexperts in the field and include both review articles thatprovide an overview of the work conducted to date andoriginal articles reporting recent discoveries and innovations.In order to highlight the translational relevance, severalpapers are focused on novel basic mechanisms as wellas clinical evidence related to atherosclerosis. In addition,papers describing the novel link between oxLDL to COPD,endometriosis, and preeclampsia are included. We hope thatthis series of papers will be beneficial for clinicians andresearchers in their diagnostic and therapeutic approachestowards inflammatory diseases. Each of the papers in thisseries is briefly highlighted as follows.

G. Maiolino et al. in the review “The role of oxidized low-density lipoproteins in atherosclerosis: the myths and the facts”examine the role played by oxidized LDLs in atherogenesistaking into account data derived by studies based onmolecu-lar and clinical approaches.The authors provide available datafrom animal models and patients cohorts that validate theoxidative modification hypothesis of atherosclerosis. Severalexperimental papers in this special issue support this view.The paper by F. Mascarenhas-Melo et al. “Implication of lowHDL-c levels in patients with average LDL-c levels: a focuson oxidized LDL, large HDL subpopulation, and adiponectin”demonstrates that in a patient populationwith cardiovascularrisk factors low HDL-c levels are associated with a poorcardiometabolic profile, despite the average levels of LDL-c. This data suggests that therapeutic interventions directedto inhibition of Ox-LDL levels and raising HDL-c levels andfunctionality are advisory preventive measures in this type ofcardiovascular risk populations.

Furthermore, J.-F. Zhao et al. in “Activation of TRPV1prevents OxLDL-induced lipid accumulation and TNF-𝛼-induced inflammation in macrophages: role of liver X receptor𝛼” demonstrate that suppression of oxLDL and activation ofLXR𝛼 by TRPV1 is protective inmacrophages.These findingsmay help in developing novel pharmacological targets fortreating atherosclerosis-related cardiovascular diseases.

Finally, J. Li et al. in “Minimally modified LDL upregulatesendothelin type A receptors in rat coronary arterial smoothmuscle cells” investigated the effects of mmLDL on theexpression of endothelin type A (ETA) receptors in coronaryarteries. The authors demonstrated that mmLDL contributes

2 Mediators of Inflammation

to the development of ischemic cardiovascular diseases byinducing an upregulation of ETA receptors in the coronaryartery. The molecular mechanisms involve the activation ofPKC and ERK1/2 MAPK pathways and the downstream NF-𝜅B signalling pathways.

The lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is the main OxLDL receptor of endothelial cells,and it is expressed also in macrophages and smooth musclecells. A. Pirillo et al. in “LOX-1, OxLDL, and atherosclero-sis” describe the evidence from mouse and humans data,suggesting that LOX-1 might be an attractive therapeutictarget for the management and the prevention of atheroscle-rosis. Inhibition of the LOX-1 receptor is currently beinginvestigated and represents an emerging approach for con-trolling OxLDL-LOX-1-mediated proatherogenic effects. Theimportant role of oxidized LDL and LOX-1 in inflam-mation is further discussed in the review “Oxidized LDLand LOX-1 in experimental sepsis” by N. Al-Banna andC. Lehmann. This review highlights the evidence relatingoxLDL and LOX-1 to proinflammatory disease mechanisms.Situations in which oxLDL is involved in disease resolu-tion due to exposure time, dose, or degree of oxidiza-tion are described. The emerging role of LOX-1 in themigration capacity of MSCs is demonstrated by F. Zhanget al. in “Ox-LDL promotes migration and adhesion ofbone marrow-derived mesenchymal stem cells via regulationof MCP-1 expression.” The authors investigated the effectsof ox-LDL on bone marrow-derived mesenchymal stemcells (bmMSCs) migration and adhesion as well as therelated mechanisms. They concluded that ox-LDL-inducedbmMSC migration and adhesion are dependent on LOX-1 activation and MCP-1 expression. This study is impor-tant since the migration capacity of MSCs is one of thedeterminants of the efficiency of MSC-based transplanttherapy.

The dual biological effect of electronegative low-densitylipoprotein (LDL (−)) which is the minor modified fractionof LDL found in blood is presented in the review “Elec-tronegative LDL: a circulating modified LDL with a role ininflammation” byM. Estruch et al.This review compares LDL(−) to oxLDL, updates findings on the inflammatory and anti-inflammatory effects of LDL (−) on cells, and discusses itsputative physiological role.

M. Gursel et al. in “Plasmacytoid dendritic cell response toCpG ODN correlates with CXCL16 expression and is inhibitedby ox-LDL” report that ox-LDL presence significantly inhib-ited D-ODN mediated IFN𝛼 production by plasmacytoiddendritic cells. Moreover the authors demonstrated thatCXCL16/CXCR6 interaction can modify the response ofpDCs to environmental danger signals.

F.J. Rios et al. in “Oxidized LDL induces alternative macro-phage phenotype through activation of CD36 and PAFR”examined the effect of oxLDL onmacrophage phenotype.Theauthors concluded that oxLDL induced macrophage differ-entiation and activation towards the alternatively activated(M2) phenotype. Furthermore, they showed that this profileof macrophage activation is dependent on the engagement ofboth CD36 and PAFR.

Among the different models of LDL oxidation that havebeen studied, the one using myeloperoxidase (MPO) isthought to be more physiopathologically relevant. K. Z.Boudjeltia et al. in “Myeloperoxidase-dependent LDL modi-fications in bloodstream are mainly predicted by angiotensinII, adiponectin, and myeloperoxidase activity: a cross-sectionalstudy in men” suggest that the combination of bloodMPO activity, angiotensin II, and adiponectin explains,at least partially, serum Mox-LDL levels. This is signif-icant since serum Mox-LDL levels are involved in thepathogenesis of atherosclerosis. Another example for theimportant role of LDL oxidation by myeloperoxidase (Mox-LDL) in the context of atherogenesis is presented byC. Delporte et al. in the review “Low-density lipopro-tein modified by myeloperoxidase in inflammatory path-ways and clinical studies.” The review focuses on acti-vation of endothelial cells and monocytes/macrophages,induction of proinflammatory molecules, and inhibiting offibrinolysis as the main mechanisms by which Mox-LDLincreases the risk of thrombus formation. Moreover, therole of Mox-LDL in the physiopathology of several dis-eases linked to atherosclerosis is also discussed. In addi-tion to atherosclerosis, the involvement of oxLDL in otherinflammatory diseases has recently emerged. G. Polak etal. in “Low-density lipoproteins oxidation and endometriosis”found that concentrations of oxLDL in peritoneal fluid ofendometriotic women were significantly higher comparedto women with serous but not dermoid ovarian cysts.Their results indicate that disrupted oxidative status inthe peritoneal cavity of women with endometriosis mayplay a role in the pathogenesis of advanced stages of thedisease. The possible relationship between COPD and ox-LDL has been investigated recently by Y. Shen et al. in“Increased serum ox-LDL levels correlated with lung func-tion, inflammation, and oxidative stress in COPD.” Theauthors describe that serum levels of ox-LDL are increasedin COPD patients and are correlated with reduced lungfunction, inflammation, and oxidative stress in COPD. S.Acikgoz et al. in “Levels of oxidized LDL, estrogens, andprogesterone in placenta tissues and serum paraoxonase activ-ity in preeclampsia” demonstrate that the events leadingto fetoplacental insufficiency lead to a reduction in thelevels of estriol limit deposition of OxLDL in placentaltissues. These observations point towards the importancerole of serum PON1 activity in the inhibition of OxLDL inpreeclampsia.

Finally, “Paraoxonase-1 inhibits oxidized low-densitylipoprotein-induced metabolic alterations and apoptosisin endothelial cells: a nondirected metabolomic study”summarized by A. Garcıa-Heredia et al. showed alterationsin carbohydrate and phospholipid metabolism and increasedapoptosis in cells incubated with oxidized LDL.These resultsextend current knowledge on the protective role of HDL andPON1 against oxidation and apoptosis in endothelial cells.

We sincerely hope that the present special issue mayprovide useful information to understand the mechanisms,the clinical effects, and the novel treatments of oxLDL-induced inflammation. We hope that the reader will findsome novel input for future researches.

Mediators of Inflammation 3

Acknowledgments

We would like to thank all contributors and reviewers fortheir excellent work, commitment, and support.

Ishak Ozel TekinAsım Orem

Ronit Shiri-Sverdlov

Submit your manuscripts athttp://www.hindawi.com

Stem CellsInternational

Hindawi Publishing Corporationhttp://www.hindawi.com Volume 2014


MEDIATORSINFLAMMATION

of


Behavioural Neurology

EndocrinologyInternational Journal of



Disease Markers


BioMed Research International

OncologyJournal of



Oxidative Medicine and Cellular Longevity


PPAR Research

The Scientific World JournalHindawi Publishing Corporation http://www.hindawi.com Volume 2014

Immunology ResearchHindawi Publishing Corporationhttp://www.hindawi.com Volume 2014

Journal of

ObesityJournal of



Computational and Mathematical Methods in Medicine

OphthalmologyJournal of


Diabetes ResearchJournal of



Research and TreatmentAIDS


Gastroenterology Research and Practice


Parkinson’s Disease

Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttp://www.hindawi.com

editorial oxidized ldl in inflammation: from bench to...

Documents