Open AccessDiabetes Impairs the Vascular Recruitment of Normal Stem Cells by Oxidant Damage, Reversed by Increases in pAMPK, Heme Oxygenase‐1, and Adiponectin
Author(s) -
Sambuceti Gianmario,
Morbelli Silvia,
Vanella Luca,
Kusmic Claudia,
Marini Cecilia,
Massollo Michela,
Augeri Carla,
Corselli Mirko,
Ghersi Chiara,
Chiavarina Barbara,
Rodella Luigi F.,
L'Abbate Antonio,
Drummond George,
Abraham Nader G.,
Frassoni Francesco
Publication year - 2009
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1634/stemcells.2008-0800
Subject(s) - copp , heme oxygenase , medicine , endocrinology , biology , enos , progenitor cell , thrombomodulin , endothelial progenitor cell , adiponectin , stem cell , nitric oxide synthase , diabetes mellitus , nitric oxide , heme , platelet , thrombin , microbiology and biotechnology , insulin resistance , biochemistry , enzyme
Background Atherosclerosis progression is accelerated in diabetes mellitus (DM) by either direct endothelial damage or reduced availability and function of endothelial progenitor cells (EPCs). Both alterations are related to increased oxidant damage. Aim We examined if DM specifically impairs vascular signaling, 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) once a week for 3 weeks. Eight weeks after the development of diabetes, EPCs harvested from the aorta of syngenic inbred normal rats and labeled with technetium‐99m‐exametazime were infused via the femoral vein to estimate their blood clearance and aortic recruitment. Circulating endothelial cells (CECs) and the aortic expression of thrombomodulin (TM), CD31, and endothelial nitric oxide synthase (eNOS) were used to measure endothelial damage. Results DM reduced blood clearance and aortic recruitment of EPCs. Both parameters were returned to control levels by CoPP treatment without affecting EPC kinetics in normal animals. These abnormalities of EPCs in DM were paralleled by reduced serum adiponectin levels, increased numbers of CECs, reduced endothelial expression of phosphorylated eNOS, and reduced levels of TM, CD31, and phosphorylated AMP‐activated protein kinase (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. S TEM C ELLS 2009;27:399–407