Phospholipase a₂ is an inflammatory predictor in cardiovascular diseases: Is there any spacious room to prove the causation?

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 glycerophos-pholipids 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 hospital-and 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.