Secretory phospholipase A2 (isoforms IIA, V, and X) (sPLA2 (IIA, V, X))

Secretory phospholipase A2 (sPLA2) isoforms IIA, V, and X are low-molecular-weight enzymes that catalyze the hydrolysis of the sn-2 ester bond of glycerophospholipids, releasing free fatty acids and lysophospholipids [3, 10]. These isoforms are key mediators of inflammation, as they provide arachidonic acid for the synthesis of pro-inflammatory eicosanoids like prostaglandins and leukotrienes [4, 6]. They are also implicated in cardiovascular disease through the remodeling of low-density lipoproteins (LDL), which promotes atherosclerosis and plaque instability [11, 12]. While initially targeted for inflammatory and cardiovascular conditions, clinical trials with inhibitors like varespladib were halted due to lack of efficacy and potential safety risks, such as an increased risk of myocardial infarction observed in the VISTA-16 trial [2, 13]. More recently, these enzymes have gained attention as targets for snakebite envenomation therapy, where they are major toxic components of venom across many species [7, 15]. They also serve as important biomarkers for disease severity in conditions like sepsis and COVID-19, where elevated levels of sPLA2-IIA correlate with poor outcomes [17, 19, 20].

Other names

sPLA2-IIAsPLA2-VsPLA2-XPLA2G2APLA2G5PLA2G10Group IIA secretory phospholipase A2Group V secretory phospholipase A2Group X secretory phospholipase A2Group 10 secretory phospholipase A2

Inhibition of the catalytic activity of secretory phospholipase A2 isoforms, preventing the hydrolysis of membrane and lipoprotein phospholipids and the subsequent release of arachidonic acid and lysophospholipids.