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Dtsch Med Wochenschr 2005; 130(12): 726-730
DOI: 10.1055/s-2005-865087
Sonderteil "Herzerkrankungen im Alter" Übersichten
Kardiologie / Pharmakologie
© Georg Thieme Verlag Stuttgart · New York

Stoffwechsel und hypertrophiertes Altersherz

Ein Indikationsziel für die Pharmakagruppe „Fettsäurenoxidationshemmer mit PPARα-Aktivierung”?Metabolism and the hypertrophied heart of the elderlyA target for the drug group „Fatty Acid Oxidation Inhibitors with PPARa Activation“?H. Rupp1 , T. P. Rupp1 , B. Maisch1
  • 1Molekular-kardiologisches Labor, Klinik für Innere Medizin und Kardiologie, Philipps-Universität Marburg, Marburg
Further Information

Publication History

eingereicht: 29.11.2004

akzeptiert: 3.3.2005

Publication Date:
18 March 2005 (online)

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Zusammenfassung

Bei älteren Patienten kommt es häufig als Folge eines nicht ausreichend behandelten Bluthochdrucks zu einer Hypertrophie der Kardiozyten, die mehrere Defekte in der Genexpression aufweisen. Es spricht vieles dafür, dass die verminderte Expression des Transkriptionsfaktors PPARα eine reduzierte Fettsäurenoxidation auslöst, die - sofern kompensatorisch die Glukoseoxidation gesteigert werden kann - als günstig eingestuft wird. Es verbleiben aber verminderte PPARα-Einflüsse auf z. B. anti-inflammatorische Mechanismen. Es stellt sich daher die Frage, ob es Pharmaka gibt, die zu einer Normalisierung reduzierter PPARα-Wirkungen führen, ohne dass die Fettsäurenoxidation gesteigert wird. Als Leitsubstanz dieser „Fettsäurenoxidationshemmer mit PPARα-Aktivierung” wurde Etomoxir, ein Hemmer der Carnitin-Palmitoyl-Transferase-1 charakterisiert, das zu einer Steigerung der Ca2+-Pumpe des sarkoplasmatischen Retikulums, einer schnelleren Relaxation und einer verlangsamten Progression der Herzinsuffizienz im Tierversuch führt. Es sollte daher geprüft werden, ob die eingeschränkte Funktion druckbelasteter hypertrophierter Kardiozyten vor allem älterer Patienten ein Therapieziel sein sollte, bevor es zur Progression der Herzinsuffizienz und Symptomen wie Kurzatmigkeit kommt.

Summary

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 PPARα, 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 PPARα influences ensue involving e. g. anti-inflammatory mechanisms. The question arises thus whether drugs can normalize reduced PPARα effects without increasing fatty acid oxidation. As lead compound of these „fatty acid oxidation inhibitors with PPARα activation”, the carnitine palmitoyltransferase-1 inhibitor etomoxir was characterized. An increased expression and activity of the Ca2+ 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.

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Prof. Dr. Heinz Rupp

Molekular-kardiologisches Labor

Karl-von-Frisch-Straße 1

35033 Marburg

Phone: 06421/2865032

Fax: 06421/2868964

Email: Rupp@staff.uni-marburg.de

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