Molecular and Cellular Events in Myocardial Hypertrophy and Failure

Abstract

Whereas cardiac failure was once thought to be a static condition reflecting a damaged myocardium, it is now apparent that it reflects a dynamic process involving the continuous structural and functional reorganization, or remodeling, of the heart in response to environmental stresses and stimuli. The fundamental events that lead to cardiac remodeling occur at the molecular and cellular level in both the myocytes and the nonmyocyte cells of the heart. Observations made in failing human myocardium and in myocardium from animals with hypertrophy or failure suggest that there are multiple molecular and cellular alterations involving the excitation-contraction process, contractile and regulatory proteins, growth factors, and signaling pathways. A variety of stimuli that may be responsible for these alterations have been identified, including mechanical wall stresses, hormones, neurotransmitters, and peptide growth factors. Genetic manipulations in small animal models are refining our understanding of the stimuli and molecular events that lead to progression of heart failure. Although much remains to be learned about how these stimuli interact with signaling pathways to regulate the remodeling of the myocardium, it is now apparent that these events have an important impact on the clinical course of the patient and may offer new approaches to the prevention and treatment of myocardial failure.