BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
Authors: Benjamin M Jackson; Joseph H Gorman; Ivan S Salgo; Sina L Moainie; Theodore Plappert; Martin St John-Sutton; L Henry Edmunds; Robert C Gorman Journal: Am J Physiol Heart Circ Physiol Date: 2002-10-31 Impact factor: 4.733
Authors: D R Pimentel; J K Amin; L Xiao; T Miller; J Viereck; J Oliver-Krasinski; R Baliga; J Wang; D A Siwik; K Singh; P Pagano; W S Colucci; D B Sawyer Journal: Circ Res Date: 2001-08-31 Impact factor: 17.367
Authors: Subhasis Chatterjee; Lawrence T Bish; Vasant Jayasankar; Allan S Stewart; Y Joseph Woo; Michael T Crow; Timothy J Gardner; H Lee Sweeney Journal: J Thorac Cardiovasc Surg Date: 2003-06 Impact factor: 5.209
Authors: Benjamin M Jackson; Joseph H Gorman; Sina L Moainie; T Sloane Guy; Navneet Narula; Jagat Narula; Martin G John-Sutton; L Henry Edmunds; Robert C Gorman Journal: J Am Coll Cardiol Date: 2002-09-18 Impact factor: 24.094