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Endothelial Dysfunction and Diabetes: Effects on Angiogenesis, Vascular Remodeling, and Wound Healing

DOI: 10.1155/2012/918267

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Abstract:

Diabetes mellitus (DM) is a chronic metabolic disorder characterized by inappropriate hyperglycemia due to lack of or resistance to insulin. Patients with DM are frequently afflicted with ischemic vascular disease or wound healing defect. It is well known that type 2？DM causes amplification of the atherosclerotic process, endothelial cell dysfunction, glycosylation of extracellular matrix proteins, and vascular denervation. These complications ultimately lead to impairment of neovascularization and diabetic wound healing. Therapeutic angiogenesis remains an attractive treatment modality for chronic ischemic disorders including PAD and/or diabetic wound healing. Many experimental studies have identified better approaches for diabetic cardiovascular complications, however, successful clinical translation has been limited possibly due to the narrow therapeutic targets of these agents or the lack of rigorous evaluation of pathology and therapeutic mechanisms in experimental models of disease. This paper discusses the current body of evidence identifying endothelial dysfunction and impaired angiogenesis during diabetes. 1. Introduction Endothelial cell dysfunction (ECD) is a broad term which implies dysregulation of endothelial cell functions, including impairment of the barrier functions of endothelial cells, vasodilation, disturbances in proliferative capacities, migratory as well as tube formation properties, angiogenic properties, attenuation of synthetic function, and deterrence of white blood cells from adhesion and diapedesis [1]. Several factors contribute to ECD including smoking, high blood pressure, diabetes, high cholesterol levels, obesity, hyperglycemia, advance glycation end products (AGEs), and genetic factors [1, 2]. Diabetes is a chronic metabolic disorder characterized by inappropriate hyperglycemia due to lack of or resistance to insulin, which contributes to ECD. About 170 million people worldwide are affected by diabetes including 20.8 million diabetic patients in the USA, numbers projected to double by 2030 [3]. Diabetes can be stratified into two groups with type 1 diabetes being insulin dependent and type II insulin independent. Both type 1 and type 2 cause hyperglycemia, which in turn causes endothelial dysfunction by its different glycooxidative products. Type 2 diabetes causes insulin resistance which is also responsible for endothelial dysfunction [4]. Obesity, which is individually a risk factor for EC dysfunction is also closely related to type 2 diabetes [5]. These two amplify the ECD more frequently. Angiogenesis or

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