Lipids and endothelial function: Effects of lipid-lowering and other therapeutic interventions

Coronary arteries are regulated by neuronal mechanisms, hormones and paracrine mediators. The importance of endothelium-dependent mechanisms has recently been recognized. The endothelium responds io mechanical and chemical signals from the blood by releasing mediators that modulate vascular tone and structure, platelet function, coagulation and monocyte adhesion. Important relaxing factors are nitric oxide, prostacyclin and a putative hyperpolarizing factor, Nitric oxide also inhibits smooth muscle proliferation and, together with prostacyclin, platelet function. Bradykinin-induced nitric oxide production is reduced by angiotensin-converting enzyme, Endothelin-1, thromboxane A(2) and prostaglandin H-2 are contracting factors. Thromboxane A(2) and prostaglandin H-2 activate platelets, while endothelin has no direct platelet effects, but causes smooth muscle proliferation. In hypercholesteremia, endothelium-dependent relaxation is impaired and contraction as well as adhesion of monocytes and platelets enhanced. Pharmacological correction of hyperlipidemia by statins also improves or normalizes endothelial dysfunction in patients. Angiotensin-converting enzyme inhibitors have similar effects.