J. Mchowat et al., Redistribution and abnormal activity of phospholipase A(2) isoenzymes in postinfarct congestive heart failure, AM J P-CELL, 280(3), 2001, pp. C573-C580
Cardiac sarcolemmal (SL) cis-unsaturated fatty acid sensitive phospholipase
D (cis-UFA PLD) is modulated by SL Ca2+-independent phospholipase A(2) (iP
LA(2)) activity via intramembrane release of cis-UFA. As PLD-derived phosph
atidic acid influences intracellular Ca2+ concentration and contractile per
formance of the cardiomyocyte, changes in iPLA(2) activity may contribute t
o abnormal function of the failing heart. We examined PLA(2) immunoprotein
expression and activity in the SL and cytosol from noninfarcted left ventri
cular (LV) tissue of rats in an overt stage of congestive heart failure (CH
F). Hemodynamic assessment of CHF animals showed an increase of the LV end-
diastolic pressure with loss of contractile function. In normal hearts, imm
unoblot analysis revealed the presence of cytosolic PLA(2) (cPLA(2)) and se
cretory PLA(2) (sPLA(2)) in the cytosol, with cPLA(2) and iPLA(2) in the SL
. Intracellular PLA(2) activity was predominantly Ca2+ independent, with mi
nimal sPLA(2) activity. CHF increased cPLA(2) immunoprotein and PLA(2) acti
vity 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 pathoph
ysiology of post-myocardial infarction CHF are abnormalities of SL PLA(2) i
soenzymes, suggesting that PLA(2)-mediated bioprocesses are altered in CHF.