Role of polyphenols in improving endothelial dysfunction in diabetes.

Endothelial cells covering the luminal surface of all blood vessels have a pivotal role in the control of vascular homeostasis mostly via the activation of protective mechanisms. These mechanisms include the endothelial formation of nitric oxide (NO) in response to the activation of endothelial NO synthase, endothelium-dependent hyperpolarization involving endothelial SKCa and IKCa, which is subsequently transmitted to the underlying vascular smooth muscle via myoendothelial junctions, and in some blood vessels, also prostacyclin. These endothelial protective mechanisms will promote vasodilatation, inhibit platelet activation, and also prevent the expression of pro-atherothrombotic factors. In most types of cardiovascular diseases including type 1 and 2 diabetes (T2D), an endothelial dysfunction as indicated by blunted endothelium-dependent vasorelaxations and often also by the appearance of endothelium-dependent cyclooxygenase-mediated contractile responses is observed early in the development of the pathology and has been suggested to contribute to the development of both macro-vascular and micro-vascular complications in T2D. The impaired endothelium-dependent relaxations in T2D has indicated the involvement of reduced NO and endothelium-dependent hyperpolarization components and is associated with increased oxidative stress in the arterial wall involving superoxide anion and hydrogen peroxide predominantly due to an up-regulation of NADPH oxidase and possibly also uncoupling of endothelial NO synthase. Investigations in experimental animals and humans have also suggested that the angiotensin system contributes to the impaired endothelial function in T2D. Several sources of polyphenols (i.e., cocoa and plant extracts) have been shown to retard the induction of endothelial dysfunction in TD2 in part by preventing oxidative stress in the arterial wall most likely by normalizing the expression of NADPH oxidase, cyclooxygenase-1 and 2, eNOS uncoupling, and the angiotensin system. Both pre-clinical and clinical data will be presented and discussed. In addition, polyphenols may possibly also improve the endothelial function by preventing the induction of endothelial senescence to high glucose and angiotensin II. Thus, polyphenols by improving the endothelial dysfunction might help to retard the development of both macro- and micro-vascular complications in diabetes.