Accumulation of arachidonic acid in ischemic/reperfused cardiac tissue: possible causes and consequences.
Under physiological conditions, the content of unesterified arachidonic acid in cardiac tissue is very low. The bulk of arachidonic acid is present in the membrane phospholipid pool. Incorporation of arachidonic acid into phospholipids (reacylation) and liberation of this fatty acid from the phospholipid pool (deacylation) are controlled by a set of finely tuned enzymes, including lysophospholipid acyltransferase and phospholipase A2. At present, at least three subtypes of phospholipase A2 have been identified in cardiac structures, i.e., a low molecular mass group II phospholipase A2, a cytoplasmic high molecular mass phospholipase A2 and a plasmalogen-specific phospholipase A2. Cessation of flow to the heart (ischemia) gives rise to net degradation of membrane phospholipids accompanied by accumulation of fatty acids, including (unesterified) arachidonic acid. Restoration of flow to the previously ischemic cells results in a continued accumulation of fatty acids. The mechanism(s) underlying net phospholipid degradation in ischemic/reperfused myocardial tissue is (are) incompletely understood. Impaired reacylation, enhanced hydrolysis of phospholipids, or a combination of both may be responsible for the phenomena observed. Elevated tissue levels of arachidonic acid may exert both direct and indirect effects on the affected myocardium and healthy cardiac cells adjacent to the injured cardiomyocytes. Indirect effects might be evoked by arachidonic acid metabolites, i.e., eicosanoids. Arachidonic acid may directly influence ion channel activity, substrate metabolism and signal transduction, thereby affecting the functional characteristics of the ischemic/reperfused myocardium.
Van der Vusse
G J
GJ
Department of Physiology, Maastricht University, Cardiovascular Research Institute Maastricht, the Netherlands. vandervusse@fys.unimaas.NL
Reneman
R S
RS
van Bilsen
M
M
D000215:Acylation; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism*; D006868:Hydrolysis; D017202:Myocardial Ischemia / Q000378:metabolism*; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000378:metabolism*; D010743:Phospholipids / Q000378:metabolism; D051381:Rats
D010743:Phospholipids; D016718:Arachidonic Acid