Nitric oxide: a key factor behind the dysfunctionality of endothelial progenitor cells in diabetes mellitus type-2

被引:80
作者
Hamed, Saher [1 ,2 ]
Brenner, Benjamin [2 ,3 ]
Roguin, Ariel [2 ]
机构
[1] Rambam Hlth Care Campus, Dept Cardiol, Haifa, Israel
[2] Technion Israel Inst Technol, Rappaport Fac Med, Cardiovasc Res Lab, IL-31000 Haifa, Israel
[3] Rambam Hlth Care Campus, Thrombosis & Hemostasis Unit, Haifa, Israel
基金
以色列科学基金会;
关键词
EPC; Nitric oxide; Diabetes mellitus; Hyperglycaemia; Hyperlipidaemia; CORONARY-ARTERY-DISEASE; LOW-DENSITY-LIPOPROTEIN; OXIDATIVE STRESS; SUPEROXIDE-DISMUTASE; ASYMMETRIC DIMETHYLARGININE; CARDIOVASCULAR RISK; ISCHEMIC-MYOCARDIUM; VASCULAR FUNCTION; PROTEIN-KINASE; CD34(+) CELLS;
D O I
10.1093/cvr/cvq412
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Diabetes mellitus type-2 (DM-2) contributes to atherogenesis by inducing endothelial cell injury and dysfunction. Endothelial progenitor cells (EPCs) are essential to blood vessel formation, can differentiate into mature endothelial cells, and promote the repair of damaged endothelium. In DM-2, the circulating EPC count is low and their functionality is impaired. The mechanisms that underlie this reduced count and impaired functionality are poorly understood. Nitric oxide (NO) is a short-lived signalling molecule that is produced by vascular endothelial cells and participates in the maintenance of vascular tone. NO is also known to participate in other physiological processes, such as cell survival, proliferation, and migration. The bioavailability of NO is reduced in EPCs from DM-2 patients. Interestingly, an inverse relationship exists between the reduction in NO bioavailability in EPCs and the patient's plasma glucose and glycated haemoglobin levels. In addition, NO bioavailability in EPCs correlates with plasma oxidized low-density lipoprotein levels in DM-2. Although this reduction in NO bioavailability could be attributed to oxidative stress in DM-2 patients, it also may be due to impairment of one or more members of the protein signalling cascades that are responsible for NO production. The stimulation of NO production or its signalling cascades in EPCs may increase their numbers and improve their function, thus attenuating endothelium damage, independent of the vasodilatory effects of NO. This review summarizes the metabolic alterations that underlie the molecular mechanisms that may be responsible for EPC decrease and dysfunction in DM-2 with emphasis on the involvement of the NO system.
引用
收藏
页码:9 / 15
页数:7
相关论文
共 71 条
[1]   Effect of diabetes mellitus on formation of coronary collateral vessels [J].
Abaci, A ;
Oguzhan, A ;
Kahraman, S ;
Eryol, NK ;
Ünal, S ;
Arinç, H ;
Ergin, A .
CIRCULATION, 1999, 99 (17) :2239-2242
[2]   Essential role of endothelial nitric oxide synthase for mobilization of stem and progenitor cells [J].
Aicher, A ;
Heeschen, C ;
Mildner-Rihm, C ;
Urbich, C ;
Ihling, C ;
Technau-Ihling, K ;
Zeiher, AM ;
Dimmeler, S .
NATURE MEDICINE, 2003, 9 (11) :1370-1376
[3]   Nitric oxide, atherosclerosis and the clinical relevance of endothelial dysfunction [J].
Anderson, TJ .
HEART FAILURE REVIEWS, 2003, 8 (01) :71-86
[4]   Isolation of putative progenitor endothelial cells for angiogenesis [J].
Asahara, T ;
Murohara, T ;
Sullivan, A ;
Silver, M ;
vanderZee, R ;
Li, T ;
Witzenbichler, B ;
Schatteman, G ;
Isner, JM .
SCIENCE, 1997, 275 (5302) :964-967
[5]   L-arginine-nitric oxide kinetics in nonnal and type 2 diabetic subjects -: A stable-labelled 15N arginine approach [J].
Avogaro, A ;
Toffolo, G ;
Kiwanuka, E ;
de Kreutzenberg, SV ;
Tessari, P ;
Cobelli, C .
DIABETES, 2003, 52 (03) :795-802
[6]   Erythropoietin regulates endothelial progenitor cells [J].
Bahlmann, FH ;
de Groot, K ;
Spandau, JM ;
Landry, AL ;
Hertel, B ;
Duckett, T ;
Boehm, SM ;
Menne, J ;
Haller, H ;
Fliser, D .
BLOOD, 2004, 103 (03) :921-926
[7]   Tetrahydrobiopterin and eNOS dimer/monomer ratio -: a clue to eNOS uncoupling in diabetes? [J].
Bauersachs, J ;
Schäfer, A .
CARDIOVASCULAR RESEARCH, 2005, 65 (04) :768-769
[8]   Asymmetric dimethylarginine, derangements of the endothelial nitric oxide synthase pathway, and cardiovascular diseases [J].
Böger, RH ;
Bode-Böger, SM .
SEMINARS IN THROMBOSIS AND HEMOSTASIS, 2000, 26 (05) :539-545
[9]   Endothelial dysfunction in obesity and insulin resistance: A road to diabetes and heart disease [J].
Caballero, AE .
OBESITY RESEARCH, 2003, 11 (11) :1278-1289
[10]   Hyperglycemia-induced reactive oxygen species and impaired endothelial progenitor cell function [J].
Callaghan, MJ ;
Ceradini, DJ ;
Gurtner, GC .
ANTIOXIDANTS & REDOX SIGNALING, 2005, 7 (11-12) :1476-1482