Diabetic angiopathy and angiogenic defects

The epidemic of obesity-associated type 2 diabetes has prompted the need for strategies to prevent and treat diabetic complications [1]. In diabetes, diverse sets of organs are damaged. Such organ damage is certainly fundamentally associated with glucose metabolism defects. Therefore, normalizing blood glucose levels is essential for diabetic therapy [2-4]. However, recent evidence suggests that normalization of blood glucose levels is challenging in diabetes, and such intensive therapies in diabetic patients are associated with increased mortality risk, likely associated with frequent hypoglycemia [5]. To this end, patients enrolled in the intensive therapy group of the ACCORD trial, which employed intensive blood glucose lowering strategies aimed to normalize blood sugar levels, exhibited increased mortality [5]. Therefore, to prevent diabetic complications, additional therapeutic strategies are required in addition to those that target blood glucose normalization.Angiopathy is a term for vascular defects that are associated with angiogenic abnormalities [6]. Understanding the precise molecular mechanisms that lead to diabetic angiopathy is essential for designing new therapeutic strategies to treat diabetic complications. In this review, we focus on diabetic vascular defects and abnormal angiogenesis.Angiogenesis is characterized by new blood vessel formation from pre-existing vessels and is distinguished from vasculogenesis, which is de novo vessel formation from hematopoietic progenitor cells [7]. Angiogenesis is essential for proper development and organ homeostasis, such as placental and embryonic growth, collateral formation, wound healing, and granulation [8]. However, angiogenesis is not always healthy and is often associated with pathologic conditions, in which case it is referred to as pathologic angiogenesis [7]. Angiogenesis results from the balanced functions of pro- and anti-angiogenic molecules (Figure？1). Defects in the angiogenic balance may cause