Lege Artis Medicinae

[Molecular mechanisms of cardiac hypertrophy and heart failure]

MIKALA Gábor1, PETŐ Mónika1, VÁLYI Nagy István1, CSÁSZÁR Albert1

OCTOBER 01, 2000

Lege Artis Medicinae - 2000;10(10)

[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 a- and B-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 Nat-Cat exchange inhibitors as one of future therapeutic agents of much promise. ]

AFFILIATIONS

  1. Semmelweis Egyetem, Egészségtudományi Kar, Belgyógyászati és Geriátriai Klinika, Budapest

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