Figure 50-5 Mechanisms involved in thrombosis and vasoconstriction at sites of atherosclerotic plaque injury resulting from plaque ulceration or fissuring caused by interventional therapy with angioplasty or stents and other injuries to endothelium. With such injury, the subendothelium is exposed, platelets adhere and aggregate, and local accumulation of mediators occurs, largely platelet derived, including thromboxane A₂ , serotonin, adenosine diphosphate, thrombin, platelet-activating factor, oxygen-derived free radicals, tissue factor, and endothelin. These mediators promote the growth of thrombus, and most are vasoconstrictors. Several mediators are also mitogens that promote fibroproliferation or exuberant scarring after endothelial injury (i.e., "restenotic lesion"). At sites of vascular injury there are reduced concentrations of normally present endogenous substances that prevent thrombosis, vasoconstriction, and inflammation, including tissue plasminogen activator (tPA), prostacyclin (PGI₂ ), and nitric oxide (tPA, PGI₂ , and endothelium-derived relaxing factor [EDRF] at top right). Loss of these normally present protective substances helps create a prothrombotic environment and one in which inflammation and fibroproliferation occur after endothelial injury. (From Willerson JT, Cohn J [eds]: Cardiovascular Medicine, 2nd ed. New York, Churchill Livingstone, 2000.)