Nipping at cardiac remodeling

Abstract

Much of the mortality following myocardial infarction results from remodeling of the heart after the acute ischemic event. Cardiomyocyte apoptosis has been thought to play a key role in this remodeling process. In this issue of the JCI, Diwan and colleagues present evidence that Bnip3, a proapoptotic Bcl2 family protein, mediates cardiac enlargement, reshaping, and dysfunction in mice without influencing infarct size.

Figure 1. Postinfarct myocardial remodeling.

Thrombotic occlusion of a coronary artery precipitates myocyte death in the ischemic zone creating a myocardial infarct (white area). The abrupt loss of functioning myocardium decreases contractile function. Acute compensation is provided by increases in left-ventricular volume (arrows) that augment function (the Frank-Starling mechanism) and neurohumoral factors that increase contractility in the noninfarcted myocardium. Augmented wall stress, a deleterious effect of increased left-ventricular volume, is reduced by myocyte hypertrophy in the noninfarcted myocardium (double-headed arrows). In addition, scar formation in the infarct limits expansion, preventing further increases in wall stress (not shown). In some patients, ventricular function is preserved. Other patients, especially those with larger infarcts, experience cardiac remodeling. In this process, the left ventricle undergoes dilation (dashed arrows), wall thinning, and a change in shape from ovoid to spherical, causing reduced contractile function and chronic heart failure. Strategies that inhibit postinfarct remodeling preserve left-ventricular geometry and function and prevent heart failure.