Fuster V, Stein B, Ambrose J A, Badimon L, Badimon J J, Chesebro J H
Division of Cardiology, Mount Sinai Medical Center, New York, NY 10029.
Circulation. 1990 Sep;82(3 Suppl):II47-59.
Rupture of an atherosclerotic plaque associated with partial or complete thrombotic vessel occlusion is fundamental to the development of ischemic coronary syndromes. Plaques that produce only mild-to-moderate angiographic luminal stenosis are frequently those that undergo abrupt disruption, leading to unstable angina or acute myocardial infarction. Plaques with increased lipid content appear more prone to rupture, particularly when the lipid pool is localized eccentrically within the intima. Macrophages appear to play an important role in atherogenesis, perhaps by participating in the uptake and metabolism of lipoproteins, secretion of growth factors, and production of enzymes and toxic metabolites that may facilitate plaque rupture. In addition, the particular composition or configuration of a plaque and the hemodynamic forces to which it is exposed may determine its susceptibility to disruption. Exposure of collagen, lipids, and smooth muscle cells after plaque rupture leads to the activation of platelets and the coagulation cascade system. The resulting thrombus may lead to marked reduction in myocardial perfusion and the development of an unstable coronary syndrome, or it may become organized and incorporated into the diseased vessel, thus contributing to the progression of atherosclerosis. In unstable angina, plaque disruption leads to thrombosis, which is usually labile and results in only a transient reduction in myocardial perfusion. Release of vasoactive substances, arterial spasm, or increases in myocardial oxygen demand may contribute to ischemia. In acute myocardial infarction, plaque disruption results in a more persistent thrombotic vessel occlusion; the extent of necrosis depends on the size of the artery, the duration of occlusion, the presence of collateral flow, and the integrity of the fibrinolytic system. Thrombi that undergo lysis expose a highly thrombogenic surface to the circulating blood, which has the capacity of activating platelets and the coagulation cascade system and may lead to thrombotic reocclusion. Measurements aimed at reversing the process of atherosclerosis via cholesterol reduction and enhanced high density lipoprotein activity are encouraging. Active research is being focused on the development of new antithrombotic tools, such as inhibitors of thrombin, thromboxane, and serotonin receptor antagonists, and monoclonal antibodies aimed at blocking platelet membrane receptors or adhesive proteins. These compounds may prove useful when immediate and potent inhibition of the hemostatic system is desired. Intensive research is still needed in the areas of pathogenesis and therapeutic intervention in atherosclerosis.
动脉粥样硬化斑块破裂伴部分或完全血栓性血管闭塞是缺血性冠状动脉综合征发生发展的根本原因。仅产生轻度至中度血管造影管腔狭窄的斑块往往是那些突然破裂的斑块，可导致不稳定型心绞痛或急性心肌梗死。脂质含量增加的斑块似乎更容易破裂，尤其是当脂质池偏心地位于内膜内时。巨噬细胞似乎在动脉粥样硬化形成中起重要作用，可能是通过参与脂蛋白的摄取和代谢、生长因子的分泌以及可能促进斑块破裂的酶和毒性代谢产物的产生。此外，斑块的特定组成或结构以及其所承受的血流动力学力可能决定其破裂的易感性。斑块破裂后胶原、脂质和平滑肌细胞的暴露会导致血小板活化和凝血级联系统激活。形成的血栓可能导致心肌灌注显著减少和不稳定冠状动脉综合征的发生，或者可能会机化并融入病变血管，从而促进动脉粥样硬化的进展。在不稳定型心绞痛中，斑块破裂导致血栓形成，血栓通常不稳定，只会导致心肌灌注短暂减少。血管活性物质的释放、动脉痉挛或心肌需氧量增加可能导致缺血。在急性心肌梗死中，斑块破裂导致更持久的血栓性血管闭塞；坏死程度取决于动脉大小、闭塞持续时间、侧支血流情况以及纤溶系统的完整性。发生溶解的血栓会使高度促血栓形成的表面暴露于循环血液中，这有激活血小板和凝血级联系统的能力，并可能导致血栓再闭塞。旨在通过降低胆固醇和增强高密度脂蛋白活性来逆转动脉粥样硬化进程的措施令人鼓舞。积极的研究正集中在开发新的抗血栓工具上，如凝血酶抑制剂、血栓素抑制剂、5-羟色胺受体拮抗剂以及旨在阻断血小板膜受体或黏附蛋白的单克隆抗体。当需要立即且强效抑制止血系统时，这些化合物可能会被证明是有用的。在动脉粥样硬化的发病机制和治疗干预领域仍需要深入研究。
