Group II secretory PLA₂: A new cardiovascular risk factor

Inflammatory mediators contribute significantly to the induction and progression of cardiovascular diseases such as atherosclerosis and acute myocardial infarction (AMI). A mediator that has been shown to play a crucial role in both cardiovascular events is group-II secretory phospholipase A₂ (sPLA₂-II), as this mediator has been suggested to modulate atherosclerotic plaque formation, for example by increasing the accumulation of intracellular lipids in macrophages and stimulating the formation of foam cells. Furthermore, increased levels of sPLA₂-II in the blood form a risk marker for the development of complications of coronary artery disease. In line with this, we recently found that extracellular sPLA₂-II is more abundantly present in the extracellular matrix of atherosclerotic culprit lesions of coronary arteries in patients who developed AMI than in those of patients with stable or unstable angina pectoris. Another important feature of sPLA₂-II is its ability to bind to and hydrolyze membrane phospholipids. Notably, sPLA₂-II cannot bind to the tightly packed hydrophobic phospholipids in the outer leaflet of a normal membrane, but only to the disarranged or flip-flopped membranes of damaged cells, as is the case in ischemic jeopardized cardiomyocytes. Interestingly, we recently have observed that sPLA₂-II cannot only bind to reversible damaged cardiomyocytes but also induces these cells to die, partly by potentiating binding of C-reactive protein and thus inducing an inflammatory response in the ischemically challenged heart. This review will discuss the pros and co ns of therapy with inhibitors of sPLA₂-II to prevent complications of the process of atherosclerosis, and/or to limit the amount of cell death of cardiomyocytes subsequent to AMI.