Phospholipase D/phosphatidic acid phosphatase signal transduction pathway in post-infarction congestive heart failure

Abstract

Post infarct congestive heart failure (CHF) is a very common clinical syndrome with high morbidity and mortality. One of the important pathophysiological characteristics is abnormalities in the CA$\sp{2+}$ homeostasis which is, in part modulated by the phospholipase D/phosphatidic acid phosphate (PLD/PAP) signaling pathway. Another pathophysiological characteristics is post infarction ventricle remodeling which is, in part, regulated by renin-angiotensin system (RAS). Angiotensin II (Ang-II) has been reported to be able to regulate phosphatidylcholine (PC)-specific PLD signal pathway. This study was designed to examine the status of the cardiac PLD/PAP signaling pathway, and observe the effect of the Angiotensin converting enzyme (ACE) inhibitor, Imidapril, on this pathway in CHF. The sarcolemmal (SL) and cytosolic PAP activity was examined by measuring the amount of sn-diacylglycerol (DAG) with labeled phosphatidic acid (PA) as substrate. A time dependent increase in SL left ventricle PLD was observed which reached a maximum at 4 weeks after ligation of coronary artery compared to the corresponding sham control values. No significant differences were found in right ventricle SL PLD activity. Similarly, a time dependent increase in the LV SL PAP activity was observed. The SL PAP activity also peaked at 4 weeks post surgery. However, in contrast, the cytosolic PAP activity peaked at 8 weeks post surgery. In the right centricle neither SL nor cytosolic PAP activities showed significant changes in CHF. In the CHF rats treated with the ACE inhibitor, Imidapril, the upregulated SL PLD activity was normalized. Furthermore, the upregulated left ventricle SL and cytocolic activities were also normalized by the Imidapril treatment. (Abstract shortened by UMI.)