Abstract 9365: Left Ventricular Dysfunction and Cardiac Hypertrophy in Kit Mutant Mice During Aging
Aim: Cardiac progenitor cells marked with c-Kit play an important role in maintaining normal cardiac function. This study aims at comparing effects of Kit mutants, including W/Wv, W41/W41, and W41/W42, on myocardial c-kit + cells profile and their association with left ventricular contractile function , hypertrophy during normal aging.
Methods: LV function of W/Wv, W41/W41 and W41/W42 mice at age of 4 months and 12 months were determined by echocardiogram using age matched wide type (WT) mice as normal controls. Bone marrow (BM) from normal donor of green fluorescent protein (GFP) marked mice, was transplanted into Kit mutant mice after irradiation to determine whether normal BM repopulation could rescue the LV dysfunction by the regeneration of myocytes from BM cells, or by promote migration of endogenous c-Kit+ progenitor cells into heart of Kit mutant mice. In addition, cardiac hypertrophy was determined and myocardial c-Kit+ cells in myocardium were quantified.
Results: Young mice with the Kit mutations showed no defects in LV functional studies in regard of LV ejection fraction (EF) and fractional shortening (FS). However EF and FS were significantly decreased in 12 months aged W41/W42 mice compared with the other three groups. Cardiac hypertrophy, indexed by heart weight/body weight was also significantly increased in W41/W42 mice compared with WT, W/Wv and W41/W41 at 12 months of age. Numbers of myocardial c-Kit+ cells were significantly reduced in all three Kit mutant mice hearts compared with WT. BM transplantation did not increase c-Kit+ progenitor cells into Kit mutated mice heart and also did not rescue decreased EF and FS of aged W41/W42 mutated mice.
Conclusions: The W41/W42 mutants show decreased LV function during normal aging that is accompanied by a significant reduction of myocardial c-Kit+ cell count. Repopulation with normal BM does not increase c-Kit+ progenitor cells in heart nor prevent reduction of LV function in aged W41/W42 mice. These data demonstrate that heart is not a post mitotic organ, and a normal myocytes turnover rate and normal LV function are supported by a pool of resident KIT+ progenitor during aging.
- © 2011 by American Heart Association, Inc.