Attuali concetti sul ruolo della disfunzione endoteliale nella patogenesi dell'arteriosclerosi ed applicazioni cliniche

Endothelium is not a mere monolayer of cells separating flowing blood and vascular wall, but plays a key role in maintenance of vascular homeostasis. Nitric oxide is the principal mediator of endothelial function; it is a potent vasodilator, it inhibits platelet aggregation, vascular smooth muscle cell migration and proliferation, and monocytes adhesion. Cardiovascular risk factors promote development of endothelial dysfunction, characterized by impairment of endothelium-dependent vasodilation (EDV) and by procoagulant/pro-inflammatory endothelial activities. The assessment of EDV is a common parameter for testing endothelial function. EDV in the coronary arteries is angiographically evaluated by measurement of the vessel response to endothelial agonists, such as acetylcholine. A non-invasive technique for the detection of EDV employs the ultrasound evaluation of flow-mediated dilation (FMD) of the brachial artery following reactive hyperemia. A close relation between FMD and coronary vasomotor response to acetylcholine has been demonstrated. Endothelial dysfunction in the coronary circulation may precede development of angiographically evident coronary atherosclerosis; endothelial dysfunction has been also associated with a higher prevalence of coronary artery disease and resulted predictive of future cardiovascular events; recently, it has been associated with a higher risk of restenosis after coronary stent implantation. Endothelial dysfunction is actually considered a reversible phenomenon; drug therapies with ACE-inhibitors, angiotensin receptor blockers, statins, antioxidants agents have shown a beneficial effect on endothelial function.