The secretory phospholipase A₂ family comprises a large range of enzymes, their main function is to hydrolyse phospholipids from the cell membrane surface and lipoproteins. sPLA₂-IIA is a prototypic member of the group II sPLA₂ subfamily and has been shown to be induced by pro-inflammatory stimuli in a wide variety of cells and tissues. It has been found to be associated with a number of inflammatory diseases including, coronary artery disease, and atherosclerosis. These factors have contributed to its nickname, “inflammatory sPLA₂” ^{1, 2}.

Fig. 1 highlights the role of sPLA₂-IIA in hydrolysing phospholipid from cell membrane surfaces, platelet-activating factor (PAF) and oxidativelymodified lipoproteins. Once hydrolysed, multiple bioactive lipids are produced including arachidonic acid which in turn is hydrolysed by cyclooxygenase to generate prostaglandins, lipoxygenase to produce lipoxines leukotriens and cytochromome P450 to generate epoxides fatty acid alcohols. In contrast, Lp-PLA₂ requires oxidised phospholipids (ox-phosphatidyl-choline) as a substrate ³.

sPLA₂-llA is already expressed in the normal arterial wall and its expression is readily up-regulated by inflammatory stimuli. Its role in producing fatty acids and biologically active phospholipids is linked to platelet, monocyte, and endothelial activation, processes known to be critical steps in atherogenesis ⁴. Research indicates that serum sPLA₂-IIA levels are higher among CAD patients than normal subjects. The lipid mediators produced through sPLA₂-IIA and their related lipids in the arterial wall can stimulate T cells and macrophages to synthesize and release the pro-atherogenic and pro-inflammatory cytokines, which in turn induce sPLA₂-IIA production in the atherosclerotic walls ⁵.

1. European Heart Journal (2019): Group IIA secretory phospholipase A₂, inflammation, and incident cardiovascular disease: An analysis from the JUPITER Trial ⁶

Objective: A study prospectively evaluated 17,802 patients enrolled in the JUPITER Trial to determine the association of sPLA₂-IIA mass with incident CVD in a primary prevention population with chronic inflammation.

Conclusion: sPLA₂-IIA plays an integral pro-inflammatory role in regulating vascular inflammation. The JUPITER trial found that elevated levels of sPLA₂-IIA at baseline was significantly associated with a greater risk of incident CVD.

2. Journal of the American College of Cardiology (2013): Secretory phospholipase A₂-IIA and cardiovascular disease: A Mendelian randomization study ⁷

Objective: A Mendelian randomisation meta-analysis prospectively examined 19 general population studies incorporating 8,021 incident, 7,513 prevalent major vascular events (MVE) in 74,684 patients and 10 acute coronary syndrome (ACS) cohorts incorporating 2,520 recurrent MVE in 18,355 patients to determine the role of sPLA₂-IIA in cardiovascular disease (CVD).

Conclusion: sPLA₂-IIA is thought to be the most highly expressed of the enzymes and observational studies have indicated that higher circulating sPLA₂-IIA mass is associated with an increased risk of CVD and MVE.