Platelets, endothelium, and vessel injury.
Injury to the endothelial lining of arteries is an important mechanism in both the early and late stages of the development of atherosclerosis. Platelets can contribute to the early lesions by releasing factors that cause smooth muscle cell migration and proliferation. In the later stages, the formation of large platelet-fibrin thrombi that become organized into the vessel wall contributes to the development of focal atherosclerotic narrowing of arteries. Injury to the vessel wall can also be a factor in causing spasm of coronary arteries, particularly at sites of stenosis. The spasm may cause ischemia, anginal pain, and, in some individuals, ventricular fibrillation and death. In other individuals, the spasm may not cause death but may persist long enough for an occlusive thrombus to form and cause myocardial infarction. The events leading to thrombosis involve not only the release of arachidonic acid and the formation of TXA2, but other pathways that are independent of the arachidonate pathway. In some circumstances thrombin (which causes platelet aggregation and release that are largely independent of the arachidonate pathway and TXA2 formation) is the primary stimulus causing the initiation and growth of the thrombus. The role of products of the arachidonate pathway in causing spasm is not understood. PGI2 produced by the vessel wall could be important in preventing or minimizing coronary artery spasm. The best way to prevent the development of atherosclerosis and its clinical complications is to prevent or minimize injury of the endothelium.
Mustard
J F
JF
Kinlough-Rathbone
R L
RL
Packham
M A
MA
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000097:blood; D001161:Arteriosclerosis / Q000150:complications / Q000503:physiopathology*; D001792:Blood Platelets / Q000502:physiology*; D002455:Cell Division; D003329:Coronary Vasospasm / Q000209:etiology; D004727:Endothelium / Q000502:physiology*; D011464:Epoprostenol / Q000096:biosynthesis / Q000494:pharmacology; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000473:pathology; D010974:Platelet Aggregation; D013927:Thrombosis / Q000150:complications; D013928:Thromboxane A2 / Q000097:blood; D014661:Vasoconstriction / Q000187:drug effects
D001095:Arachidonic Acids; D016718:Arachidonic Acid; D013928:Thromboxane A2; D011464:Epoprostenol