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Atherosclerosis or lipoprotein-induced endothelial dysfunction. Potential mechanisms underlying reduction in EDRF/nitric oxide activity.

1992; Lippincott Williams & Wilkins; Volume: 85; Issue: 5 Linguagem: Inglês

10.1161/01.cir.85.5.1927

1524-4539

Nicholas A. Flavahan,

Cardiovascular Health and Disease Prevention

Activation of endothelial cells by physical, chemi- cal, and hormonal stimuli can result in the release of a number of vasoactive mediators.1Under physiological conditions, mediator release ap- pears to be balanced in favor of inhibitory factors such as endothelium-derived relaxing factor (EDRF, identified as nitric oxide) and prostacyclin (PGI2) (Figure 1).'-3EDRF-NO and PGI have important protective actions in the vascular wall: They are potent inhibitors of smooth muscle contraction and smooth muscle proliferation,14 and they also inhibit platelet aggregation, stimulate platelet disaggregation, and inhibit platelet or monocyte adhesion to the endothelial surface.25,6The endothelial cells located at sites that are prone to atherosclerosis appear to be morphologically and functionally different from normal endothelial cells.7-10These endothelial cells have a diminished protective role in the blood vessel wall and may actively promote the atherosclerotic process.8Numerous studies have demonstrated that a dysfunction in the release of EDRF-NO appears to occur at an early stage in the atherosclerotic process in animals and hu- mans.'1-23This impairment in EDRF-NO release may be associated with an increased release of endotheliumderived contracting factors (EDCFs),18'24 which are func- tional and chemical antagonists of 1).The shift in the balance of endothelial mediators might contribute in part to the diminution in the protec- tive role of the endothelium and could predispose the blood vessel to vasospasm or to a further progression of the disease process.Previous studies have demonstrated that the impairment in endothelial dilator activity that occurs in ath- erosclerotic or hypercholesterolemic blood vessels re- flects an impairment in the ability of the cells to respond to specific stimuli.Thus, in a number of different arterial preparations (Table 1), hypercholesterolemia did not affect the endothelium-dependent relaxations evoked by certain stimuli, e.g., A23187, but caused