Mechanisms of endothelial dysfunction: clinical significance and preventive non-pharmacological therapeutic strategies.

Endothelium-derived NO is not only a potent vasodilator but also inhibits platelet aggregation, vascular smooth muscle cell migration and proliferation, monocyte adhesion and adhesion molecule expression, thus protecting the vessel wall against the development of atherosclerosis. Cardiovascular risk factors are associated with an imbalance of the redox equilibrium towards oxidative stress and, therefore, impair the integrity of the endothelium, leading to endothelial activation which involves blunted endothelium-dependent vasodilation (vasodilator dysfunction) as well as inflammatory processes extending to the milieu within the whole vasculature, making plaques prone to rupture. In prospective studies endothelial dysfunction is associated with increased incidence of cardiovascular events. Thus, the prevention of endothelial dysfunction can determine a strong advantage in the clinical outcome of patients with cardiovascular risk factors. Several non-pharmacological interventions can prevent endothelial dysfunction or improve impaired endothelium-dependent vasodilation. Probably the most effective non-pharmacological measure is represented by aerobic physical activity, which can reduce production of oxidative stress associated to increasing age. Moreover, physical activity can improve endothelial dysfunction even in patients with cardiovascular risk factors such as essential hypertension. In addition several other approaches, including vitamin and fish oil supplementation, or tea and red wine consumption, can lead to an improvement of endothelium-dependent vasodilation, possibly by a restoration of NO availability. It is worth noting that most of non-pharmacological measures act by preventing or reducing oxidative stress.