Redistribution and abnormal activity of phospholipase A(2) isoenzymes in postinfarct congestive heart failure.
Cardiac sarcolemmal (SL) cis-unsaturated fatty acid sensitive phospholipase D (cis-UFA PLD) is modulated by SL Ca(2+)-independent phospholipase A(2) (iPLA(2)) activity via intramembrane release of cis-UFA. As PLD-derived phosphatidic acid influences intracellular Ca(2+) concentration and contractile performance of the cardiomyocyte, changes in iPLA(2) activity may contribute to abnormal function of the failing heart. We examined PLA(2) immunoprotein expression and activity in the SL and cytosol from noninfarcted left ventricular (LV) tissue of rats in an overt stage of congestive heart failure (CHF). Hemodynamic assessment of CHF animals showed an increase of the LV end-diastolic pressure with loss of contractile function. In normal hearts, immunoblot analysis revealed the presence of cytosolic PLA(2) (cPLA(2)) and secretory PLA(2) (sPLA(2)) in the cytosol, with cPLA(2) and iPLA(2) in the SL. Intracellular PLA(2) activity was predominantly Ca(2+) independent, with minimal sPLA(2) activity. CHF increased cPLA(2) immunoprotein and PLA(2) activity in the cytosol and decreased SL iPLA(2) and cPLA(2) immunoprotein and SL PLA(2) activity. sPLA(2) activity and abundance decreased in the cytosol and increased in SL in CHF. The results show that intrinsic to the pathophysiology of post-myocardial infarction CHF are abnormalities of SL PLA(2) isoenzymes, suggesting that PLA(2)-mediated bioprocesses are altered in CHF.
McHowat
J
J
Department of Pathology, St. Louis University Medical School, St. Louis, Missouri 63104, USA. mchowatj@slucare1.sluh.edu
Tappia
P S
PS
Liu
S
S
McCrory
R
R
Panagia
V
V
D000818:Animals; D002118:Calcium / Q000502:physiology; D003600:Cytosol / Q000201:enzymology; D006333:Heart Failure / Q000201:enzymology* / Q000209:etiology*; D006352:Heart Ventricles; D008297:Male; D009203:Myocardial Infarction / Q000150:complications*; D009206:Myocardium / Q000201:enzymology; D010741:Phospholipases A / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D012508:Sarcolemma / Q000201:enzymology; D014018:Tissue Distribution
D010741:Phospholipases A; D002118:Calcium