Sunday, September 11, 2011

Lipoprotein-associated Phospholipase A2 (Lp-PLA2) as a Marker of Rapture Prone Atherosclerotic Plaque

Lipoprotein-associated phospholipase A2 (Lp-PLA2) is an enzyme that has attracted considerable attention of the researchers and cardiologists as a predictor of atheroma prone for rapture; which can give rise to catastrophic cardiovascular events.
Diabetes, smoking; and high low density lipoproteins (LDL) popularly known as bad cholesterol apart from many more; are the most important risk factors for heart attacks or ischaemic heart disease (IHD).
There are some predictors of cardiovascular risks like C - reactive protein and Fibrinogen levels in the blood, those correlates with high risk of atherosclerosis. Now, determining the Lipoprotein-associated phospholipase A2 in the blood has been seen to have better predictive value for rapture prone atherosclerotic plaques.
It is not the atherosclerotic plaques per se, rather rapture of the plaque that causes the sudden cardiac events. The ruptured plaque can block arteries of heart and cut off blood supply to the part supplied by those.
Increase in the blood level of Lp-PLA2 can predict the vulnerability of the plaque to rapture.
It is an enzyme secreted by some blood cells e.g. macrophages in a response to the inflammation produced by the oxidized LDL. It’s level kept unregulated by the chronic low level of inflammation.
This enzyme is also carried by the oxidized-LDL particles in the blood circulation. Endothelial dysfunction loosens the tight junctions between the cells of the inner layer, the endothelium of the vessel wall that allows the LDL to enter inside.
Below the endothelium this enzyme causes the degradation of the oxidized LDL through a process called hydrolysis to LysoPC (Lysophosphatidyl choline) and NEFA (Non-esterified fatty acids).
These products attract the macrophages in addition to triggering several other pathways to cause necrosis of the core of the plaque, which may eventually become unstable and rapture.
Inhibitor of Lp-PLA2 enzyme like darapladib has been seen to decrease the cardiac events.
ATP III Guideline:
PLAC is a commercially available test approved by the FDA to measure the blood level of Lp-PLA2. The rising level warrants reduction of blood LDL level by LDL lowering drugs according to Adult Treatment Panel III (ATP III) guideline.

Algorithm of PLAC test and Implications:
Pa-PLA2 1
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