Document Detail

Alterations of sarcolemmal phospholipase D and phosphatidate phosphohydrolase in congestive heart failure.
MedLine Citation:
PMID:  12213494     Owner:  NLM     Status:  MEDLINE    
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.
Chang-Hua Yu; Vincenzo Panagia; Paramjit S Tappia; Song-Yan Liu; Nobuakira Takeda; Naranjan S Dhalla
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Biochimica et biophysica acta     Volume:  1584     ISSN:  0006-3002     ISO Abbreviation:  Biochim. Biophys. Acta     Publication Date:  2002 Sep 
Date Detail:
Created Date:  2002-09-05     Completed Date:  2002-10-29     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0217513     Medline TA:  Biochim Biophys Acta     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  65-72     Citation Subset:  IM    
Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, Winnipeg, Manitoba, Canada.
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MeSH Terms
Angiotensin-Converting Enzyme Inhibitors / therapeutic use
Coronary Stenosis
Disease Models, Animal
Enzyme Activation / drug effects
Guanosine 5'-O-(3-Thiotriphosphate) / pharmacology
Heart Failure / drug therapy,  enzymology*
Heart Ventricles / drug effects
Imidazoles / therapeutic use
Myocardium / enzymology*
Oleic Acid / pharmacology
Phosphatidate Phosphatase / analysis,  metabolism*
Phosphatidylinositol 4,5-Diphosphate / pharmacology
Phospholipase D / analysis,  metabolism*
Rats, Sprague-Dawley
Sarcolemma / drug effects,  enzymology
Time Factors
Reg. No./Substance:
0/Angiotensin-Converting Enzyme Inhibitors; 0/Imidazoles; 0/Imidazolidines; 0/Phosphatidylinositol 4,5-Diphosphate; 112-80-1/Oleic Acid; 37589-80-3/Guanosine 5'-O-(3-Thiotriphosphate); 89396-94-1/imidapril; EC Phosphatase; EC D

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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