bone marrow support of the heart in pressure overload is lost with aging骨髓支持心脏的压力过载与老化失去.pdfVIP

Bone Marrow Support of the Heart in Pressure Overload Is Lost with Aging 1,2,3 2 2 2 2,3 Nikolai A. Sopko , Benjamin A. Turturice , Mitchell E. Becker , Chase R. Brown , Feng Dong , ´4, Marc S. Penn2,3,4* Zoran B. Popovic 1 Case Western Reserve University School of Medicine, Cleveland, Ohio, United States of America, 2 Skirball Laboratory for Cardiovascular Cellular Therapeutics, Cleveland Clinic, Cleveland, Ohio, United States of America, 3 Department of Stem Cell Biology and Regenerative Medicine, Cleveland Clinic, Cleveland, Ohio, United States of America, 4 Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, Ohio, United States of America Abstract Rationale: Exogenous stem cell delivery is under investigation to prevent and treat cardiac dysfunction. It is less studied as to the extent endogenous bone marrow derived stem cells contribute to cardiac homeostais in response to stress and the affects of aging on this stress response. Objective: To determine the role of bone marrow (BM) derived stem cells on cardiac homeostasis in response to pressure overload (PO) and how this response is altered by aging. Methods and Results: Young (8 weeks) and old (.40 weeks) C57/b6 mice underwent homo- and heterochronic BM transplantation prior to transverse aortic constriction (TAC). We found that older BM is associated with decreased cardiac function following TAC. This decreased function is associated with decrease in BM cell engraftment, increased myocyte apoptosis, decreased myocyte hypertrophy, increased myocardial fibrosis and decreased cardiac function. Additionally, there is a decrease in activa