Abstract 1275: Cardiomyocyte Specific Overexpression of Stem Cell Factor Improves Cardiac Function and Survival post Myocardial Infarction in Mice
Background: Stem cell factor (SCF) has two isoforms, a soluble and a membrane associated protein. Exogenous SCF administration has been shown to mobilize bone marrow stem cells and improve cardiac repair post-myocardial infarction (MI). However, the direct effect of SCF on cardiac remodeling post-MI is not known. The present study investigated the effects of cardiomyocyte specific overexpression of the membrane isoform of human SCF on cardiac function post-MI.
Methods and Results: A novel transgenic mouse model was generated in which the membrane isoform of human SCF is expressed in cardiomyocytes using an alpha-myosin heavy chain and tetracycline-transactivating factor (tTA)-regulated promoter. MI was induced by left coronary artery ligation in hSCF-tTA transgenic and wild-type (WT) mice. Mortality was monitored for 30 days. Cardiac function was determined in vivo using a pressure-volume system (see Table⇓, * P<0.05, ** P<0.01 vs. WT). Cardiac function was significantly improved in hSCF-tTA mice at 5 and 30 days post-MI. LV volume and myocyte size 30 days post-MI were decreased in hSCF-rTA compared to WT mice with no significant difference in infarct size. Myocardial apoptosis assessed by cell death ELISA and caspase-3 activity 5 days post-MI was significantly decreased in hSCF-tTA compared to WT mice (P<0.05). Thirty day mortality was significantly decreased in hSCF-tTA compared to WT mice (8/43 vs. 17/32, p<0.01).
Conclusions: Cardiomyocyte specific overexpression of SCF improves myocardial function and survival post-MI. These beneficial effects of SCF may result from decreases in myocardial apoptosis and cardiac remodeling.