Signaling effectors underlying pathologic growth and remodeling of the heart
Jop H. van Berlo, … , Marjorie Maillet, Jeffery D. Molkentin
Jop H. van Berlo, … , Marjorie Maillet, Jeffery D. Molkentin
Published January 2, 2013
Citation Information: J Clin Invest. 2013;123(1):37-45. https://doi.org/10.1172/JCI62839.
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Category: Review Series

Signaling effectors underlying pathologic growth and remodeling of the heart

Abstract

Cardiovascular disease is the number one cause of mortality in the Western world. The heart responds to many cardiopathological conditions with hypertrophic growth by enlarging individual myocytes to augment cardiac pump function and decrease ventricular wall tension. Initially, such cardiac hypertrophic growth is often compensatory, but as time progresses these changes become maladaptive. Cardiac hypertrophy is the strongest predictor for the development of heart failure, arrhythmia, and sudden death. Here we discuss therapeutic avenues emerging from molecular and genetic studies of cardiovascular disease in animal models. The majority of these are based on intracellular signaling pathways considered central to pathologic cardiac remodeling and hypertrophy, which then leads to heart failure. We focus our discussion on selected therapeutic targets that have more recently emerged and have a tangible translational potential given the available pharmacologic agents that could be readily evaluated in human clinical trials.

Authors

Jop H. van Berlo, Marjorie Maillet, Jeffery D. Molkentin

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Figure 1

Overview of different types of cardiac hypertrophy.

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Overview of different types of cardiac hypertrophy. The normal heart can...
The normal heart can develop different types of hypertrophic remodeling depending on the stress. Exercise and pregnancy result in physiologic hypertrophy, in which individual cardiomyocytes increase in length and width and the heart undergoes a balanced type of eccentric hypertrophy (chambers, walls, and septum enlarge in unison). Pathologic stress or hypertrophic cardiomyopathy activates neuroendocrine factors that stimulate cardiac hypertrophy, often resulting in concentric remodeling, in which cardiomyocytes mostly increase in width compared with length, resulting in wall and septal thickening and a loss of chamber area. Over time, this state can deteriorate into dilated and eccentric hypertrophy, in which individual cardiomyocytes reduce in width and lengthening becomes excessive, leading to extreme chamber enlargement with loss of wall and septal thickness, along with large increases in wall tension. Some disease states can lead directly to dilated cardiomyopathy without a prior concentric remodeling phase.