Apoptosis--new opportunities for novel therapeutics for heart diseases

Cardiovascular Drugs and Therapy
G Z Feuerstein

Abstract

Apoptosis as defined by contemporary science describes a form of cell death that involves discrete genetic and molecular programs, de novo protein expression and unique cellular phenotype. Evidence for the existence of apoptosis in the human heart has been reported in various cardiac diseases, including ischemic and non-ischemic heart failure, myocardial infarction and arrhythmias. Among the most potent stimuli that elicit cardiomyocyte apoptosis are: oxygen radicals (including NO), cytokines, (e.g., TNFalpha, FAS) neurohormonal factors (angiotension II), cardiotoxic drugs (e.g., doxorubicin) and mechanical, stretch situations. Several complex signal transduction pathways have been implicated in execution of cardiomyocyte apoptosis. Most prominent are: 1) Tyrosine kinase receptors (TRK) induced signaling involving stress or mitogen activated protein kinases (SAPK/MARK) and sphingolipids metabolites (ceramide); 2) G-protein coupled receptor (GPCR) signaling (Galphai, Galphaq) and 3) NF(K) B activation. Apoptosis of cardiac myocytes may contribute to progressive pump-failure, arrhythmias and cardiac remodeling. The recognition of diverse molecular targets associated with cardiomyocyte apoptosis provide new opportunities for pharm...Continue Reading

Citations

Mar 20, 2004·Expert Review of Cardiovascular Therapy·María A FortuñoJavier Díez
May 4, 2004·Journal of Biochemical and Molecular Toxicology·Sherif Y SaadMouied Alashari
Jul 15, 2015·Journal of Cardiovascular Pharmacology·Huiying ZhaoChengwen Sun
May 29, 2018·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Shuang WangRuixia Qiu
May 12, 2004·Free Radical Biology & Medicine·Yudong WangK Murali Krishna Rao

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