Alterations of sarcolemmal phospholipase D and phosphatidate phosphohydrolase in congestive heart failure.
Phospholipase D 2 (PLD2) is the major PLD isozyme associated with the cardiac sarcolemmal (SL) membrane. Hydrolysis of SL phosphatidylcholine (PC) by PLD2 produces phosphatidic acid (PA), which is then converted to 1,2 diacylglycerol (DAG) by the action of phosphatidate phosphohydrolase type 2 (PAP2). In view of the role of both PA and DAG in the regulation of Ca(2+) movements and the association of abnormal Ca(2+) homeostasis with congestive heart failure (CHF), we examined the status of both PLD2 and PAP2 in SL membranes in the infarcted heart upon occluding the left coronary artery in rats for 1, 2, 4, 8 and 16 weeks. A time-dependent increase in both SL PLD2 and PAP2 activities was observed in the non-infarcted left ventricular tissue following myocardial infarction (MI); however, the increase in PAP2 activity was greater than that in PLD2 activity. Furthermore, the contents of both PA and PC were reduced, whereas that of DAG was increased in the failing heart SL membrane. Treatment of the CHF animals with imidapril, an angiotensin-converting enzyme (ACE) inhibitor, attenuated the observed changes in heart function, SL PLD2 and PAP2 activities, as well as SL PA, PC and DAG contents. The results suggest that heart failure is associated with increased activities of both PLD2 and PAP2 in the SL membrane and the beneficial effect of imidapril on heart function may be due to its ability to prevent these changes in the phospholipid signaling molecules in the cardiac SL membrane.
Yu
Chang-Hua
CH
Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, Winnipeg, Manitoba, Canada.
Panagia
Vincenzo
V
Tappia
Paramjit S
PS
Liu
Song-Yan
SY
Takeda
Nobuakira
N
Dhalla
Naranjan S
NS
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000818:Animals; D023921:Coronary Stenosis; D004195:Disease Models, Animal; D004789:Enzyme Activation / Q000187:drug effects; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D006333:Heart Failure / Q000188:drug therapy / Q000201:enzymology*; D006352:Heart Ventricles / Q000187:drug effects; D007093:Imidazoles / Q000627:therapeutic use; D048289:Imidazolidines; D008297:Male; D009206:Myocardium / Q000201:enzymology*; D019301:Oleic Acid / Q000494:pharmacology; D010711:Phosphatidate Phosphatase / Q000032:analysis / Q000378:metabolism*; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000494:pharmacology; D010739:Phospholipase D / Q000032:analysis / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012508:Sarcolemma / Q000187:drug effects / Q000201:enzymology; D013997:Time Factors
D000806:Angiotensin-Converting Enzyme Inhibitors; D007093:Imidazoles; D048289:Imidazolidines; D019269:Phosphatidylinositol 4,5-Diphosphate; D019301:Oleic Acid; D016244:Guanosine 5'-O-(3-Thiotriphosphate); C065166:imidapril; D010711:Phosphatidate Phosphatase; D010739:Phospholipase D