Potential Role of Phospholipase A2 in the Normoxic, Ischemic, and Reperfused Heart

Abstract

Phospholipids constitute an essential part of such biological membranes as the sarcolemma and intracellular membranes of cardiac muscle cells and thus contribute to the maintenance of cardiomyocyte integrity. Phospholipids are subject to continuous turnover, the deacylation—reacylation cycle. Membrane phospholipids also represent an important source of substrates for the production of biologically active compounds, including arachidonic acid and lysophospholipids. Arachidonic acid may serve as the substrate for production of biologically active eicosanoids. Phospholipase A2 plays a crucial role in the deacylation—reacylation cycle and generation of biologically active compounds, emphasizing its importance in signaling pathways. In cardiac tissue, at least three different types of phospholipase A2 have been identified: group II phospholipase A2, plasmalogen-selective Ca2+-independent phospholipase A2, and the cytosolic arachidonoyl-selective phospholipase A2. It is incompletely understood whether these types of cardiac phospholipase A2 are equally important in the phospholipid deacylation-reacylation cycle and signal transduction. Under pathophysiological conditions such as ischemia and reperfusion, the normally finely tuned turnover of membrane phospholipids is out of balance. In energy-depleted cells, degradation of phospholipids prevails over resynthesis. Consequently, lysophospholipids and arachidonic acid accumulate in the energy-deprived tissue. Although not definitively proven, both plasmalogen-selective phospholipase A2 and group II phospholipase A2 are thought to be instrumental in ischemia-induced membrane phospholipid hydrolysis. It remains to be shown, however, whether phospholipase A2-mediated phospholipid degradation is playing a crucial role in the sequelae of events leading to ischemic cell death rather than representing an epiphenomenon occurring in the irreversibly damaged cells. Experiments with hearts of genetically modified mice are currently being performed to provide answers to this as yet unresolved issue.