Lipoprotein-associated
phospholipase A2 clinical application
Physiological and biochemical characteristics
Lipoprotein-associated
phospholipase A2 (Lp-PLA2), a platelet-activating factor
acetylhydrolase, is a type of phospholipase that is closely related to
arteriosclerosis and ischemic cardiovascular and cerebrovascular
diseases in recent years. A2 superfamily, a new inflammatory marker and an independent risk factor. Which has the role of proinflammatory, so the production and release
of Lp-PLA2 from inflammatory cells can also be interpreted as an
excellent pre-inflammatory response indicators.
Lp-PLA2 is encoded by PLA2G7 and contains 441 amino acids with a molecular weight of 45 kDa. In blood, Lp-PLA2 is mainly transported along with LDL, and less than 20% of Lp-PLA2 is associated with HDL. Lp-PLA2 mainly inflammatory cells, such as macrophage secretion, can be hydrolyzed LDL oxidized phospholipids.
Lp-PLA2
produces oxidative molecules in the vessel wall, which are more prone
to cause atherosclerosis and produce unstable plaques. Elevated
levels of Lp-PLA2 are a significant risk of plaque formation and
rupture, and are independent of other lipids and CRP levels. By
detecting the level of Lp-PLA2 in the circulatory system, it is
possible to independently predict the pathogenesis of cardiovascular and
cerebrovascular diseases. Human
plasma Lp-PLA2 relative molecular mass of 50000, mainly by mature
macrophages and lymphocytes synthesis and secretion, and by the
regulation of inflammatory mediators, human circulation of Lp-PLA in
lipoprotein particles with the form of binding, in which 2/3 and LDL binding, 1/3 and HDL, VLDL binding u. There was a positive correlation between plasma Ip-PLA2 activity and Lp-PLA2 concentration. Lp-PLA
can hydrolyze platelet activating factor (PAF) to make it inactive, it
is also known as platelet-activating factor acetylhydrolase (PAF-AH). But
the enzyme substrate specificity is not strong, in addition to
hydrolysis of PAF, but also hydrolysis of LDL on the oxidation of
lecithin to produce lysolecithin and oxidized free fatty acids, the
latter two are pro-inflammatory mediators, by stimulating adhesion
factors and cytokines Generation,
and promote monocytes from the lumen to the inner membrane aggregation,
derived from macrophages, macrophages engulfed oxidized LDL into foam
cells, foam cells gathered into atherosclerotic plaques, plaques in the
cytokines and proteases The role of ulcers or rupture, thrombosis and cardiovascular events. Therefore, theoretically Lp-PLA. With the promotion of atherosclerosis and the occurrence of cardiovascular events.
Clinical application
1, Lp-PLA2 and coronary heart disease
Lp-PLA2
was found to be strongly expressed in the necrotic core and surrounding
macrophages of vulnerable plaques and ruptured plaques, and was
relatively difficult to detect in stable plaques, suggesting that
Lp-PLA2 potentially promotes plaques Instability. The direct consequence of plaque instability is an increased risk of cardiovascular disease. Plasma
Lp-PLA2 activity in patients with coronary heart disease was
significantly higher than non-coronary heart disease patients, but in
patients with stable angina and acute coronary syndrome no significant
difference. This shows that plasma Lp-PLA2 activity can reflect the severity of
coronary atherosclerotic lesions, and coronary artery disease stability
has nothing to do.
With
the change of coronary blood flow and the response of coronary artery
diameter to intracoronary acetylcholic acid as the evaluation criteria
of endothelial function, it was found that with the concentration of
plasma Lp-PLA2, the coronary blood flow was significantly decreased and
epicardial coronary artery Acetylcholic acid reactive contraction significantly enhanced. Therefore, Lp-PLA2 is also an independent predictor of coronary artery endothelial dysfunction.
2, Lp-PLA2 and atherosclerosis
Recent
studies have shown that atherosclerosis (As) is an inflammatory disease
that is involved in the development of atherosclerotic plaque
formation, as well as loss of stability and atherosclerotic plaques Rupture shedding plays an important role. Inflammatory response is one of the important mechanisms of As formation. At
the early stage of atherosclerosis, Lp-PLA2 is produced in the coronary
circulation, and the subsequent lyso-lecithin is associated with
coronary endothelial dysfunction. Therefore, plasma Lp-PLA2 can be used as a marker of atherosclerotic risk. In addition, Lp-PLA2 levels in different regions and populations are
consistent with cardiovascular and cerebrovascular risk, which makes the
potential role of Lp-PLA2 in the clinical cardiovascular and
cerebrovascular events as eye-catching as possible therapeutic targets.
3, Lp-PLA2 and ischemic stroke
Recently,
several large epidemiological and clinical prospective studies have
found that plasma Lp-PLA2 concentration or activity of ischemic stroke
is an independent risk factor. Elevated plasma Lp-PLA2 patients, coronary heart disease events and the risk of ischemic stroke increased significantly. In addition, Lp-PLA2 can be a good predictor of stroke recurrence risk.
Principles of clinical application
Normal reference value: 8-150 ng / ml
>
150 ng / ml suggest increased atherosclerotic plaque instability,
increased risk of cardiovascular and cerebrovascular diseases.