Effects of insulin resistance on endothelial progenitor cells and vascular repair.
Insulin resistance, a key feature of obesity, the metabolic syndrome and Type 2 diabetes mellitus, results in an array of metabolic and vascular phenomena which ultimately promote the development of atherosclerosis. Endothelial dysfunction is intricately related to insulin resistance through the parallel stimulatory effects of insulin on glucose disposal in metabolic tissues and NO production in the endothelium. Perturbations characteristic of insulin resistance, including dyslipidaemia, inflammation and oxidative stress, may jeopardize the structural or functional integrity of the endothelium. Recent evidence suggests that endothelial damage is mitigated by endogenous reparative processes which mediate endothelial regeneration. EPCs (endothelial progenitor cells) are circulating cells which have been identified as mediators of endothelial repair. Several of the abnormalities associated with insulin resistance, including reduced NO bioavailability, increased production of ROS (reactive oxygen species) and down-regulation of intracellular signalling pathways, have the potential to disrupt EPC function. Improvement in the number and function of EPCs may contribute to the protective actions of evidence-based therapies to reduce cardiometabolic risk. In the present article, we review the putative effects of insulin resistance on EPCs, discuss the underlying mechanisms and highlight potential therapeutic manoeuvres which could improve vascular repair in individuals with insulin resistance.
Cubbon
Richard M
RM
Division of Cardiovascular and Diabetes Research, Leeds Institute of Genetics, Health & Therapeutics (LIGHT) and the Multidisciplinary Cardiovascular Research Centre, University of Leeds, U.K.
Kahn
Matthew B
MB
Wheatcroft
Stephen B
SB
D054392:Adipokines / Q000502:physiology; D000818:Animals; D002450:Cell Communication / Q000502:physiology; D064987:Cell- and Tissue-Based Therapy / Q000379:methods; D003924:Diabetes Mellitus, Type 2 / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D003925:Diabetic Angiopathies / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D042783:Endothelial Cells / Q000502:physiology*; D004730:Endothelium, Vascular / Q000502:physiology; D013006:Growth Hormone / Q000502:physiology; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D007328:Insulin / Q000502:physiology; D007333:Insulin Resistance / Q000502:physiology*; D007334:Insulin-Like Growth Factor I / Q000502:physiology; D008019:Life Style; D024821:Metabolic Syndrome / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D051379:Mice; D009569:Nitric Oxide / Q000502:physiology; D009765:Obesity / Q000473:pathology / Q000503:physiopathology; D047492:Peroxisome Proliferator-Activated Receptors / Q000819:agonists; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000187:drug effects; D012307:Risk Factors; D013234:Stem Cells / Q000502:physiology*
D054392:Adipokines; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007328:Insulin; D047492:Peroxisome Proliferator-Activated Receptors; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone