aging kit mutant mice develop cardiomyopathy老化设备突变小鼠发展心肌病.pdfVIP

Aging Kit Mutant Mice Develop Cardiomyopathy 1,2. 1,3. 1 3 1 1 Lei Ye , Eric Yang Zhang , Qiang Xiong , Clinton M. Astle , Pengyuan Zhang , Qinglu Li , 1 3 . 1,2 . Arthur H. L. From , David E. Harrison * , Jianyi Jay Zhang * 1 Leilihei Heart Institute, Department of Medicine, University of Minnesota Medical School, Minneapolis, Minnesota, United States of America, 2 Stem Cell Institute, University of Minnesota, Minneapolis, Minnesota, United States of America, 3 The Jackson Laboratory, Bar Harbor, Maine, United States of America Abstract Both bone marrow (BM) and myocardium contain progenitor cells expressing the c-Kit tyrosine kinase. The aims of this study were to determine the effects of c-Kit mutations on: i. myocardial c-Kit+ cells counts and ii. the stability of left ventricular (LV) contractile function and structure during aging. LV structure and contractile function were evaluated (echocardiography) in two groups of Kit mutant (W/Wv and W41/W42) and in wild type (WT) mice at 4 and 12 months of age and the effects of the mutations on LV mass, vascular density and the numbers of proliferating cells were also determined. In 4 month old Kit mutant and WT mice, LV ejection fractions (EF) and LV fractional shortening rates (FS) were comparable. At 12 months of age EF and FS were significantly decreased and LV mass was significantly increased only in W41/W42 mice. Myocardial vascular densities and c-Kit+ cell numbers were significantly reduced in both mutant groups when compared to WT hearts. Replaceme