Lp-PLA2: Specific Marker for Vascular inflammation

Asst.Prof. Pilaiwan Siripurkpong

Faculty of Allied Health Sciences,

Thammasat University

Contents

• Acute coronary syndrome (ACS)

• Inflammation marker in ACS (Atherosclerosis progression/Plaque rupture)

• C-reactive protein

• Lipoprotein Phospholipase A2 (LpPLA2)

• LpPLA2 in clinical use (NCEP)

Acute Coronary Syndrome

Acute Coronary Syndrome (ACS)

Acute Coronary syndrome: ACS

Blood tests to detect inflammation

• ESR, CRP and PV can be raised in many inflammatory conditions - for example:– Certain infections (mainly bacterial infections).– Abscesses.– Certain types of arthritis.– Various other muscular and connective tissue disorders -

for example, polymyalgia rheumatica or temporal arteritis.– Tissue injury and burns.– Cancers.– Crohn's disease.– Rejection of an organ transplant.– Heart attack.

Erythrocyte Sedimentation Rate (ESR)

• Rate at which the red blood cells separate from the plasma and fall to the bottom of a test tube

• Measured in millimetres per hour (mm/hr)

• Fibrinogen levels go up which causes RBC to clump

http://www.google.co.th/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&docid=D0D_x6GD3SmNLM&tbnid=VU9fqVol-QGowM:&ved=0CAUQjRw&url=http://neuros.org/index.php?option%3Dcom_topics%26view%3Dtopic%26id%3D36900%26alias%3Desr&ei=zLuCU-GLIpKeugTf_IKgCw&bvm=bv.67720277,d.c2E&psig=AFQjCNGz6MeNKj4YjN_FuNnvfcwe_oI8LQ&ust=1401162939568801

C-reactive protein (CRP)

• CRP measures general inflammation in your body.

• High levels of CRP are caused by infections and many long-term diseases.

• CRP test cannot show where the inflammation is located or what is causing it.

http://www.google.co.th/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&docid=Fg6z0dXZqwDaBM&tbnid=FHk0rSpgmxmQrM:&ved=0CAUQjRw&url=http://vdilab.com/page.php?id%3D78&ei=Tc11U6mcH86jugTwsILACQ&bvm=bv.66699033,d.c2E&psig=AFQjCNFnTO-PMWd1w-g6n9Oz3A1w6JBhCA&ust=1400315251069975

Functional CRP pathways

Rhodes, B. et al. (2011) C-reactive protein in rheumatology: biology and geneticsNat. Rev. Rheumatol. doi:10.1038/nrrheum.2011.37

https://www.drjockers.com/2014/03/measuring-c-reactive-protein-levels/

C-Reactive Protein

CRP and ESR

Comparison of ESR and CRP

Results affected by ESR CRP

Gender Yes No

Age Yes No

Pregnancy Yes No

Temperature Yes No

Drugs (eg. steroids, salicylates)

Yes No

Smoking Yes No

CRP test is done to:• Check for infection after surgery: Normally rise within 2 - 6

hours of surgery and then go down by the third day after surgery.

• Identify and keep track of infections and diseases that cause inflammation, such as: – Cancer of the lymph nodes (lymphoma).

– Diseases of the immune system, such as lupus.

– Painful swelling of the blood vessels in the head and neck (giant cell arteritis).

– Painful swelling of the tissues that line the joints (rheumatoid arthritis).

– Swelling and bleeding of the intestines (inflammatory bowel disease).

– Infection of a bone (osteomyelitis).

• To check how well treatment is working: CRP levels go up quickly and then become normal quickly if you are responding to treatment measures.

CRP test

• One problem with the CRP test is that

– It's not specific, so levels can be elevated due to other sources of inflammation besides artherosclerosis, such as gum disease or a viral infection.

– Lowering CRP levels doesn't necessarily reduce risk of heart disease.

• CRP Test Not Recommended for Everyone

High-sensitivity CRP (hs-CRP)

• Hs-CRP may be done to find out if you have an increased chance of having a sudden heart problem, such as a heart attack.

• Inflammation can damage the inner lining of the arteries and make having a heart attack more likely.

High-sensitivity CRP (hs-CRP)

Lipoprotein phospholipase A2 (Lp-PLA2)

A biomarker of future risk of cardiovascular disease

Lipoprotein phospholipase A2 (Lp-PLA2)

• Lp-PLA2 is a 45-kDa protein, 441 amino acids, a calcium-independent member of the phospholipase A2 family

• Also known as platelet-activating factor acetylhydrolase(PAF-AH)

• In human plasma, the majority of the Lp-PLA2activity is present as a complex with LDL and lipoprotein(a).

• In human atherosclerotic lesions, 2 main sources of Lp-PLA2

can be identified, including that which is brought into the intima bound to LDL (from the circulation), and that which is synthesized de novo by plaque inflammatory cells (macrophages, T cells, mast cells).

http://www.springerimages.com/Images/RSS/1-10.1007_s13167-011-0063-4-1

LpPLA2 activity

Products from LpPLA2 activity

1. Polyunsaturated fatty acid: to form various eicosanoids and eicosanoid related mediators

2. Lysophospholipids such as lysophosphatidylcholine may also serve as markers of local Lp-PLA2 activity

Role of LpPLA2 in atherosclerosis

http://www.springerimages.com/Images/RSS/1-10.1007_s12170-009-0073-0-0

Kolodgie F D et al. Arterioscler Thromb Vasc Biol2006;26:2523-2529.

Staining intensity for Lp-PLA2 withProgression to Plaque Rupture

Christie Ballantyne, MD, Circulation. 2004; 109:837-842 Gorelick, PB. Am J Cardiol. 2008 Jun 16;101(12A):34F-40F

The controversial role of Lp-PLA2.

Münzel T , and Gori T Eur Heart J 2009;30:2829-2831

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2009. For permissions please email: journals.permissions@oxfordjournals.org

Lp-PLA2

https://bd7f7fd5a7-custmedia.vresp.com/library/1303939771/e9c164cf65/arteries2.jpg

PLAC® test for Lp-PLA2

The US Food and Drug Administration (FDA) approved theimmunoassay test PLAC (diaDexus Inc, South San Francisco, CA)

for screening of patients with high CVD risk.

Conclusion

• Lp-PLA2 is potentially a marker of vascular inflammation, a risk factor, a prognostic biomarker, and ultimately a target of therapy.

• The true role of Lp-PLA2 in atherogenesis-as a mediator, a defence mechanism, or a bystander-will need to be investigated.

• Lp-PLA2 is most clinically useful if its measurement will modify therapy

• Lp-PLA2 is most appropriately applied in patients with elevated levels that result in more aggressive management of CVD risk factors