Abstract
This study examined effects of diabetes mellitus (DM) on cellular proliferation associated with vascular endothelial growth factor (VEGF) signaling in endothelial progenitor cells (EPCs) and evaluated protein expression involved in cellular proliferation and proapoptotic signaling in chronically ischemic myocardium. Insulin-dependent DM was induced in yucatan miniswine with alloxan. Eight weeks after induction, chronic ischemia was induced by ameroid constrictor placement around the circumflex coronary artery. Seven weeks after ameroid constrictor, perfusion of ischemic territory was measured by isotope-labeled microspheres, and ischemic myocardium was harvested. Bone marrow (BM) samples were harvested from iliac bone and mononuclear cells (MNCs) were cryopreserved. EPCs were isolated from cryopreserved MNCs in control (n = 6) and DM swine (n = 6). EPC proliferation was assessed. EPC proliferation was decreased in DM as compared to control (1.02 ± 0.09, 0.40 ± 0.04, p < 0.01). VEGF-induced EPC proliferation was impaired in DM as compared to control (p < 0.01). Expression of ERK protein, an activator of VEGF-induced cell proliferation, was decreased. AKT activation, an inhibitor of apoptosis, was decreased, while Bad, an activat...Continue Reading
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