Istituto di Fisiologia Clinica     
Sambuceti G., Morbelli S., Vanella L., Kusmic C., Marini C., Massollo M., Augeri C., Corselli M., Ghersi C., Chiavarini B., Rodella L. F., L'Abbate A., Drummond G., Abraham N. A., Frassoni F. Diabetes Impairs the Vascular Recruitment of Normal Stem Cells by Oxidant Damage; Reversed by Increases in pAMPK, Heme Oxygenase-1 and Adiponectin. In: Stem Cells, vol. epub nov 2008 article n. 10.1634/stemcells.2008-0. Alpha Med Press, 2008.
Background: Atherosclerosis progression is accelerated in diabetes (DM) either by direct endothelial damage or a reduction in availability and function of endothelial progenitor cells (EPCs). Both alterations are related to increased oxidant damage. Aim: We examined if DM specifically impairs vascular signalling thereby reducing the recruitment of normal EPCs, and if increases in antioxidant levels by induction of heme oxygenase-1 (HO-1) can reverse this condition. Methods: Control and diabetic rats were treated with the HO-1 inducer cobalt protoporphyrin (CoPP,0.5 mg/100 g/bw) once a week for three weeks. Eight weeks after development of diabetes 2 X106 EPCs harvested from aorta of syngenic inbred normal rats and labelled with 1.85 MBq of 99mTc-exametazime were infused via the femoral vein to estimate their blood clearance and aortic recruitment. Circulating endothelial cells and the aortic expression of thrombomodulin, CD31 and eNOS measured endothelial damage. Results: DM reduced blood clearance and aortic recruitment of EPCs. Both parameters were returned to control levels by CoPP treatment without affecting EPCs kinetics in normal animals. These abnormalities of EPCs in DM were paralleled by reduced serum adiponectin levels, increased numbers of circulating endothelial cells, reduced endothelial expression of peNOS, reduced levels of thrombomodulin (TM), CD31 and pAMPK. CoPP treatment restored all of these parameters to normal levels. Conclusion: Type II DM and its related oxidant damage hamper the interaction between the vascular wall and normal EPCs by mechanisms that are, at least partially, reversed by the induction of HO-1 gene expression, adiponectin and pAMPK levels.
DOI: 10.1634/stemcells.2008-0800
Subject stem cells
hemeoxygenase 1
oxidative damage

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