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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: 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
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.
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/
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.
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: [email protected]
Lp-PLA2
https://bd7f7fd5a7-custmedia.vresp.com/library/1303939771/e9c164cf65/arteries2.jpg
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