Mechanotransduction in Cardiac Hypertrophy and Ischemia

Abstract

Mechanotransduction is the process by which load-bearing cells sense physical forces, transduce the forces into biochemical signals, and generate adaptive or maladaptive responses that lead to alterations in cell structure and function. Mechanotransduction in the heart not only affects the beat-to-beat regulation of cardiac performance, but also profoundly affects the growth, differentiation, and survival of the cellular components that comprise the human myocardium. Understanding the molecular basis for mechanotransduction is, therefore, important to our overall understanding of growth regulation and function during cardiac hypertrophy and ischemia. Cardiomyocytes rely on several intracellular components to sense mechanical load, and convert mechanical stimuli into biochemical events that affect cellular structure and function. These sensors include protein components within the myofilaments and Z-discs, integrins and other membrane-associated proteins that link the extracellular matrix to the cytoskeleton, and stretch-activated ion channels. A complex signaling web then transmits signals from mechanosensors to the nucleus and other organelles. Ultimately, it is hoped that new pharmacological and molecular genetic approaches targeted to specific components of the mechanotransduction machinery will be developed to translate this wealth of basic knowledge into therapeutic strategies designed to reduce cardiac hypertrophy, further protect the ischemic myocardium, and prevent its transition to heart failure.