Infarction induced myocardial apoptosis and ARC activation

Apoptosis is thought to play a role in infarction induced ventricular remodeling. Apoptosis repressor with caspase recruitment domain (ARC) has been shown to limit cardiomyocytes apoptosis; however, its role in the pathogenesis of heart failure is not established. This study examines the regional and temporal relationships of apoptosis, ARC, and remodeling.

Myocardium was harvested from the infarct borderzone and remote regions of the left ventricle (LV) at 2 (n=8), 8 (n=6), and 32 (n=5) wk after MI. Activated ARC was compared with myocardial apoptosis in each region at each time. Both were then compared with the progression of remodeling.

LV systolic volume increased by a factor 1.56±0.06 and 2.09±0.07 at 2 and 8 wk, respectively then stabilized by 32 wk (2.08±0.18). Activated ARC was elevated at 2 wk, diminished at 8 wk, and increased again at 32 wk in both regions. Apoptosis was elevated at 2 wk, and further increased at 8 wk. By 32 wk, apoptosis had diminished significantly.

In a large animal infarction model, remodeling varied directly with the degree of apoptosis and inversely with ARC activation, suggesting that ARC acts as a natural regulatory phenomenon that limits apoptosis induced ventricular remodeling.