Monroe V Stephen, Kerensky Richard A, Rivera Enrique, Smith Karen M, Pepine Carl J
Division of Cardiovascular Medicine, University of Florida College of Medicine, Gainesville, Florida 32610, USA.
J Am Coll Cardiol. 2003 Feb 19;41(4 Suppl S):23S-30S. doi: 10.1016/s0735-1097(02)02774-2.
Acute coronary syndrome (ACS) is often associated with the rupture of vulnerable atherosclerotic plaque, coronary thrombus formation, and abrupt limitation of blood flow, leading to adverse outcomes. Passivation of vulnerable plaque represents a therapeutic concept that has the potential to prevent or limit the magnitude of a new rupture in order to reduce the recurrence or severity of events. Plaque passivation can be defined as a process by which the structure or content of the atherosclerotic plaque is changed to reduce the risk of subsequent rupture and thrombosis. This may be achieved by using strategies that address different components of the plaque or the endothelium. The following factors can affect the susceptibility of plaque to rupture: macrophage infiltration; accumulation of inflammatory cells; paracrine secretion of enzymes that may cause degradation of the fibrous cap of coronary plaque; shear stress; circadian rhythm variation in stress hormone release; and infectious agents. The use of pharmacologic agents to reduce plaque vulnerability by passivation has been explored. Clinical studies demonstrate that lipid-modifying agents (e.g., statins), antiplatelet agents (acetylsalicylic acid, thienopyridines, thianopyridines, glycoprotein IIb/IIIa inhibitors), and antithrombotic agents (unfractionated heparin and low-molecular-weight heparin) can reduce the occurrence of acute coronary events in ACS patients. In addition, angiographic studies suggest that statins may also promote regression of atherosclerosis. Angiotensin-converting enzyme inhibitors, niacin, and calcium antagonists may also contribute to plaque passivation. This article reviews atherosclerotic plaque development and vulnerability and discusses some clinical studies highlighting the role of plaque passivation in the management of ACS patients.
急性冠状动脉综合征（ACS）通常与易损动脉粥样硬化斑块破裂、冠状动脉血栓形成及血流突然受限相关，进而导致不良后果。易损斑块的钝化是一种治疗理念，有可能预防或限制新的破裂程度，以降低事件的复发率或严重程度。斑块钝化可定义为改变动脉粥样硬化斑块结构或成分以降低后续破裂和血栓形成风险的过程。这可通过针对斑块或内皮不同成分的策略来实现。以下因素可影响斑块破裂的易感性：巨噬细胞浸润；炎症细胞积聚；可能导致冠状动脉斑块纤维帽降解的酶的旁分泌；剪切应力；应激激素释放的昼夜节律变化；以及病原体。人们已探索使用药物通过钝化来降低斑块易损性。临床研究表明，调脂药物（如他汀类药物）、抗血小板药物（乙酰水杨酸、噻吩吡啶类、糖蛋白IIb/IIIa抑制剂）和抗血栓药物（普通肝素和低分子量肝素）可降低ACS患者急性冠状动脉事件的发生率。此外，血管造影研究表明他汀类药物还可能促进动脉粥样硬化的消退。血管紧张素转换酶抑制剂、烟酸和钙拮抗剂也可能有助于斑块钝化。本文综述了动脉粥样硬化斑块的发展和易损性，并讨论了一些突出斑块钝化在ACS患者管理中作用的临床研究。
