Molecular Mechanisms of Diabetes Mellitus–Induced Dysfunction of the Angiogenic Competence Diabetes Mellitus and Hypoxia-Related Pathways

In patients with type 1 (T1D) and type 2 diabetes mellitus (T2D), cardiovascular disease is the most common cause of death, 45% and 52%, respectively. In particular, diabetes mellitus is associated with microand macrovascular complications resulting in coronary heart disease and increased morbidity and mortality. Similarly, patients with diabetes mellitus are at high risk for peripheral arterial disease characterized by symptoms of intermittent claudication or critical limb ischemia (CLI). These vascular complications include both qualitative and quantitative adjustments of the vascular architecture. In particular, the negative outcome of patient with diabetes mellitus is partly related to the abrogation of new vessel formation and remodeling of the pre-existing vasculature that represent an integral component of tissue remodeling and control the extent of ischemic injury. In addition, vascular dysfunction, mainly characterized by alteration of the mechanical properties of the arterial wall and functional disruption of the endothelium, is associated with diabetes mellitus and likely fuel the pathogenesis of vascular disease in T1D and T2D. Therefore, the present review focuses on the molecular mechanisms involved in the vascular defects associated with diabetes mellitus–induced postischemic vessel growth in the setting of myocardial infarction (MI) or CLI. Molecular Mechanisms of Diabetes Mellitus–Induced Dysfunction of the Angiogenic Competence Diabetes Mellitus and Hypoxia-Related Pathways