Protein kinase signaling at the crossroads of myocyte life and death in ischemic heart disease

Ronald J. Vagnozzi, Nicholas E. Hoffman, John W. Elrod, Muniswamy Madesh, Thomas Force

Research output: Contribution to journalReview articlepeer-review

4 Scopus citations

Abstract

Myocardial ischemia results in death of cardiac myocytes via tightly regulated and interconnected signaling pathways. Protein kinases play crucial roles in this regulation and are highly amenable to therapeutic intervention, making targeted inhibition an attractive strategy for ischemic heart disease. Recent studies have uncovered numerous kinases that participate in the cardiomyocyte response to ischemic injury, thus potentiating the development of new therapeutics. Moreover, many kinase signaling pathways converge at the mitochondria, a key participant in both cardiomyocyte physiology and the pathogenesis of ischemic heart disease. Herein we highlight kinase pathways regulating three major drivers of cell death: mitochondrial permeability transition pore opening (mPTP), programmed necrosis and Ca2+ overload-induced mitochondrial dysfunction. Inhibition of each of these kinase pathways has been proposed as a means to limit cardiomyocyte death from ischemia/reperfusion (I/R) injury.

Original languageEnglish (US)
Pages (from-to)e173-e182
JournalDrug Discovery Today: Therapeutic Strategies
Volume9
Issue number4
DOIs
StatePublished - 2012
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology
  • Drug Discovery

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