“Endothelial Protector Drugs” and Diabetes: Is there a Role for these Drugs?

Abstract

Diabetic vasculopathy, including macro and micro vascular disorders, is the leading cause of morbidity and mortality in patients with type 1 (T1) and type 2 (T2) diabetes mellitus (DM) [1]. A lot of researches pointed out that endothelial dysfunction, characterized by an imbalance between Endothelium-Derived Relaxing Factors (EDRFs) and endothelium-derived contracting factors (EDCFs) play a central role on the development and progression of diabetic vasculopathy [2-5]. Endothelial dysfunction and inflammation, as indicated by abnormal flow-dependent vasodilatation and by increased circulating levels of adhesion molecules (ICAM-1 and E-selectin) are known to occur in T2DM and seems to be an important predictor in systemic atherogenesis [6]. Both hyperglycemia and insulin administration increasing circulating levels of endothelin-1 (ET-1), an endothelial cell (EC)-derived potent vasoconstrictor peptide with mitogenic, pro-oxidative and pro-inflammatory properties that have shown to be extremely relevant to the pathophysiology of diabetic vasculopathy [7-10]. Circulating and local levels of ET-1 are increased in diabetic animal models and diabetic patients [1,11,12].