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.