ASSA14-03-28 Cellular repressor of E1A-stimulated genes improves heart function in a mouse model of MI

Abstract

Backgroud Cellular repressor of E1A-stimulated genes (CREG) is a mannose-6-phosphate-containing secreted glycoprotein of 220 amino acids. It has been proposed that CREG acts as a ligand that enhances differentiation and/or reduces cell proliferation. In humans, the potential therapeutic role of embryonic stem cells (ESCs) in ischaemic heart disease is subject to intense investigation. Particularly, the contribution of ESCs to angiogenesis and cardiomyogenesis in myocardial ischemia is not well established. In our studies, we induced myocardial infarct (MI) in mouse model, and monitored the effects of ESCs transplantation of overexpression of CREG on cardiac function. Methods pCXN2-Flag-wtCREG, pCXN2-Flag-mutCREG and pCXN2-Flag-EGFP plasmids were transfected into ESCs by lipofectamine 2000. Coronary artery ligation to induce MI model in seven- to nine-week-old mice was developed by a novel and rapid surgical method. wtCREG, mutCREG and EGFP ESCs or DMEM were then injected into the peri-ischaemic area. Four groups of mice were analysed for haemodynamic and pathologic parameters 1 and 2 months after MI and injection. Results The heart weight to body weight ratio was also significantly decreased at day 28 (5.9 ± 0.5 and 5.5 ± 0.4) in comparison with control hearts (7.0 ± 0.5, p Conclusions Therefore, the expression of CREG improves cardiac functions and inhibits birosis and apoptosis. These data suggest that a key mechanism of the protective effects of ASK1 in reducing ischaemic injury is via maintaining the classic proapoptotic factor Bax in an inactive state.