Phospholipase A2 is an Inflammatory Predictor in Cardiovascular Diseases: Is there any Spacious Room to Prove the Causation?

Abstract

Lipoprotein-associated phospholipase A2 (Lp-PLA2) is an enzyme family of phospholipase A2 produced by the inflammatory cell in atherosclerotic plaque. It is transported in the circulation, attached mainly to low-density lipoprotein-cholesterol (LDL-C). It hydrolyzes glycerophospholipids particularly fatty acids at the sn-2 position and produces numerous bioactive lipids; and leads to endothelial dysfunction, atherosclerotic plaque inflammation, and development of the necrotic core in plaques. There are two kinds of phospholipase A2, namely: secretory phospholipase A2 (sPLA2) and Lp- PLA2. They are deemed as evolving predictors of cardiovascular disease (CVD) risk in hospitaland population-based studies, including healthy subjects, acute coronary syndromes (ACS) and patients with CVD. Unfortunately, Lp-PLA2 inhibitor (darapladib) and s-PLA2 inhibitor (varespladib methyl) failed to prove to lower the risk of composite CVD mortality, myocardial infarction and stroke in those with stable CVD and ACS. Herein, we describe the explanation based on the existing data why there is still a discrepancy among them. So, it highlights the opinion that phospholipase A2 is merely the inflammatory biomarkers of CVD and playing an important role in atherosclerosis. Further, there is more spacious room to prove the causation.

Keywords: LDL-C; Lipoprotein-associated phospholipase A2; acute coronary syndromes; atherosclerosis; cardiovascular disease; myocardial infarction..

Fig. (1)

Phospholipase A2 enzymatic activity generates lipid products with biological properties and functions [16]. (A higher resolution / colour version of this figure is available in the electronic copy of the article).

Fig. (2)

Pathogenic role of lipoprotein-associated phospholipase A2 in atherosclerosis development [25]. (A higher resolution / colour version of this figure is available in the electronic copy of the article).

Fig. (3)

Enzymatic reaction of PAF – AH. PAF-AH: platelet-activating factor ~ acetyl hydrolase [40]. (A higher resolution / colour version of this figure is available in the electronic copy of the article).

Fig. (4)

Structure of PAF-AH in mammals. PAH-AH or Lp-PLA2 is a heterotetrameric enzyme consisting of catalytic 29- and 30- kDa and non-catalytic 45-kDa subunits [40]. (A higher resolution / colour version of this figure is available in the electronic copy of the article).

Fig. (5)

V279F polymorphism of PLA2G7 gene in Asian and Caucasian population [60]. (A higher resolution / colour version of this figure is available in the electronic copy of the article).

Fig. (6)

R92H polymorphism of PLA2G7 gene in Asian and Caucasian population [60]. (A higher resolution / colour version of this figure is available in the electronic copy of the article).