[Metabolism and the hypertrophied heart of the elderly].
In elderly patients, an inadequately treated high blood pressure often leads to hypertrophied cardiomyocytes with various defects in gene expression. Due to a decreased expression of the transcription factor PPARalpha, fatty acid oxidation is reduced. If it can be compensated by an increased glucose oxidation, it has been considered as a favorable process. Nonetheless, reduced PPARalpha influences ensue involving e. g. anti-inflammatory mechanisms. The question arises thus whether drugs can normalize reduced PPARalpha effects without increasing fatty acid oxidation. As lead compound of these "fatty acid oxidation inhibitors with PPARalpha activation", the carnitine palmitoyltransferase-1 inhibitor etomoxir was characterized. An increased expression and activity of the Ca (2+) pump of sarcoplasmic reticulum, a faster relaxation and a slowed progression of heart failure was observed in animal experiments. It should, therefore, be examined whether the impaired function of pressure overloaded hypertrophied cardiomyocytes of particularly elderly patients should be a therapeutic target before progression of heart failure, neuroendocrine activation and symptoms such as shortness of breath occur.
Rupp
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H
Molekular-kardiologisches Labor, Klinik für Innere Medizin und Kardiologie, Philipps-Universität Marburg, Marburg. Rupp@staff.uni-marburg.de
Rupp
T P
TP
Maisch
B
B
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000172:deficiency / Q000502:physiology; D006332:Cardiomegaly / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D002334:Carnitine O-Palmitoyltransferase / Q000037:antagonists & inhibitors*; D004734:Energy Metabolism / Q000187:drug effects / Q000235:genetics*; D004852:Epoxy Compounds / Q000627:therapeutic use*; D005227:Fatty Acids / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D006333:Heart Failure / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D006439:Hemodynamics / Q000235:genetics / Q000502:physiology; D006801:Humans; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D009200:Myocardial Contraction / Q000235:genetics / Q000502:physiology; D009206:Myocardium / Q000378:metabolism*; D010084:Oxidation-Reduction / Q000187:drug effects; D047493:PPAR alpha / Q000235:genetics* / Q000502:physiology; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases
D001786:Blood Glucose; D004852:Epoxy Compounds; D005227:Fatty Acids; D000960:Hypolipidemic Agents; D047493:PPAR alpha; D002334:Carnitine O-Palmitoyltransferase; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000252:Calcium-Transporting ATPases; C054207:etomoxir