title: Diabetes mellitus and ischemic diseases: molecular mechanisms of vascular repair dysfunction.
abstract: In patients with diabetes mellitus, the ability of ischemic tissue to synchronize the molecular and cellular events leading to restoration of tissue perfusion in response to the atherosclerotic occlusion of a patent artery is markedly impaired. As a consequence, adverse tissue remodeling and the extent of ischemic injury are intensified, leading to increased morbidity and mortality. Growing evidence from preclinical and clinical studies has implicated alterations in hypoxia-inducible factor 1 levels in the abrogation of proangiogenic pathways, including vascular endothelial growth factor A/phosphoinositide 3' kinase/AKT/endothelial nitric oxide synthase and in the activation of antiangiogenic signals characterized by accumulation of advanced glycation end products, reactive oxygen species overproduction, and endoplasmic reticulum stress. In addition, the diabetic milieu shows a switch toward proinflammatory antiregenerative pathways. Finally, the mobilization, subsequent recruitment, and the proangiogenic potential of the different subsets of angiogenesis-promoting bone marrow-derived cells are markedly impaired in the diabetic environment. In this review, we will give an overview of the current understanding on the signaling molecules contributing to the diabetes mellitus-induced impairment of postischemic revascularization mainly in the setting of myocardial infarction or critical limb ischemia.
authors.affiliation: From the INSERM UMRS 970, Paris Descartes University, Sorbonne Paris Cité, Paris, France.
authors.forename: Kiave Yune
authors.initials: KY
authors.lastname: Howangyin
authors.affiliation: From the INSERM UMRS 970, Paris Descartes University, Sorbonne Paris Cité, Paris, France. jean-sebastien.silvestre@inserm.fr.
authors.forename: Jean-Sébastien
authors.initials: JS
authors.lastname: Silvestre
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000502:physiology; D002465:Cell Movement; D003925:Diabetic Angiopathies / Q000503:physiopathology*; D042783:Endothelial Cells / Q000166:cytology; D017127:Glycation End Products, Advanced / Q000502:physiology; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000502:physiology; D007249:Inflammation / Q000503:physiopathology; D007511:Ischemia / Q000503:physiopathology*; D035683:MicroRNAs / Q000502:physiology; D018919:Neovascularization, Physiologic; D017382:Reactive Oxygen Species / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology
chemical_list: D017127:Glycation End Products, Advanced; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D035683:MicroRNAs; D017382:Reactive Oxygen Species; D042461:Vascular Endothelial Growth Factor A
keywords: angiogenesis; anoxia; diabetes mellitus; inflammation; intercellular signaling peptides and proteins; ischemia; stem cells