A szivizom-hypertrophia es a szivelegtelenseg molekularis mechanizmusai

Translated title of the contribution: Molecular mechanisms of cardiac hypertrophy and heart failure

G. Mikala, M. Peto, I. Valyi-Nagy, A. Császár

Research output: Contribution to journalArticle

Abstract

In this review, the most important molecular mechanisms leading to cardiac muscle hypertrophy and consequentially to heart failure are detailed. In numerous instances, understanding molecular mechanisms offers the possibility for pharmacotherapeutic intervention. First, trimeric G-proteins and their attached intracellular signaling pathways are introduced, with special emphasis on the pathways elucidated by transgenic animal models. In this area, there are several clinically effective drugs to influence cardiac hypertrophy, including ACE-inhibitors, angiotensin receptor antagonists, as well as α- and β-adrenergic receptor blockers. Mitogen activated protein kinases participate later in the hypertrophic cascade. There are ongoing investigations on the potential therapeutic use of lipid-soluble statins - these are indirect inhibitors of Ras-farnesylation. Altered cellular Ca2+-homeostasis is fundamental with respect to cardiac muscle hypertrophy and heart failure. The third part of this article investigates the role of the calcium/calmodulin dependent protein phosphatase called calcineurin in these processes. Administration of cyclosporin A or tacrolimus (both are inhibitors of calcineurin) may not be recommended in most forms of cardiac hypertrophy, however, in certain settings they may prove to be valuable therapeutic agents. One of the most serious, not yet properly addressed problem of late stage heart failure is the development of ventricular arrhythmias caused by repolarization abnormalities. Certain mechanisms of this phenomenon are highlighted with a special note on Na+-Ca+ exchange inhibitors as one of future therapeutic agents of much promise.

Original languageHungarian
Pages (from-to)754-763
Number of pages10
JournalLege Artis Medicinae
Volume10
Issue number10
Publication statusPublished - 2000

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Cardiomegaly
Heart Failure
Myocardium
Prenylation
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Genetically Modified Animals
Adrenergic Antagonists
Calcineurin
Angiotensin Receptor Antagonists
Phosphoprotein Phosphatases
Tacrolimus
Therapeutic Uses
Calmodulin
Mitogen-Activated Protein Kinases
GTP-Binding Proteins
Angiotensin-Converting Enzyme Inhibitors
Adrenergic Receptors
Cyclosporine
Cardiac Arrhythmias
Homeostasis

ASJC Scopus subject areas

  • Medicine(all)

Cite this

A szivizom-hypertrophia es a szivelegtelenseg molekularis mechanizmusai. / Mikala, G.; Peto, M.; Valyi-Nagy, I.; Császár, A.

In: Lege Artis Medicinae, Vol. 10, No. 10, 2000, p. 754-763.

Research output: Contribution to journalArticle

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