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Effects of Diabetes Mellitus on VEGF‐Induced Proliferation Response in Bone Marrow Derived Endothelial Progenitor Cells
Author(s) -
Mieno Shigetoshi,
Boodhwani Munir,
Robich Michael P.,
Clements Richard T.,
Sodha Neel R.,
Sellke Frank W.
Publication year - 2010
Publication title -
journal of cardiac surgery
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.428
H-Index - 58
eISSN - 1540-8191
pISSN - 0886-0440
DOI - 10.1111/j.1540-8191.2010.01086.x
Subject(s) - medicine , progenitor cell , vascular endothelial growth factor , endothelial progenitor cell , bone marrow , protein kinase b , cell growth , endocrinology , cancer research , signal transduction , stem cell , microbiology and biotechnology , biology , vegf receptors , genetics
Background: 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. Methods: 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. Results: 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 activator of proapoptotic signaling, was elevated in the ischemic myocardium from DM. Collateral dependent perfusion was impaired in DM. Conclusion : Impaired VEGF‐induced proliferation response in EPC as well as an increase in negative myocardial protein expression for cell proliferation and proapoptotic signaling via VEGF could be a therapeutic target to enhance the effects of proangiogenesis therapies in DM and other chronic illnesses . (J Card Surg 2010;25:618‐625)