Adams P C, Badimon J J, Badimon L, Chesebro J H, Fuster V
Cardiovasc Clin. 1987;18(1):49-71.
There is now considerable evidence to suggest that some aspects of early lesion formation and later lesion growth are a reaction to injury. Hemodynamic factors are important in determining the site of injury and may produce injury directly. Injury can lead to atherogenesis in animal models as well as in humans. Superficial injury exposes the subendothelium, allowing platelet adhesion, which at high shear rates is dependent on vWF. Platelet adhesion and degranulation release PDGF, which stimulates smooth muscle cell proliferation, synthetic functions, and vasoconstriction. LDL stimulates smooth muscle cell growth as well as damages endothelium in some experimental systems. Thus, a link is provided between platelet and lipid involvement in atherosclerosis. Direct evidence for a role of platelets in atherogenesis comes from studies in which animals were treated to reduce platelet number or function or in which platelet function is genetically impaired (pigs with von Willebrand's disease). In these models, reduced platelet function is associated with less atherosclerosis. Deeper injury exposes collagen, with subsequent platelet aggregation, thrombin and fibrin generation. The role of reduced production of PGI2 and fibrinolytic agents following severe damage is unknown. Deep injury to the vessel occurs during plaque fissuring, the pathologic process underlying most cases of myocardial infarction, unstable angina, and some cases of sudden death. Angioplasty produces amelioration of many patients' symptoms and is safe. However, acute occlusion occurs occasionally, and restenosis in the first year occurs in some 30 percent of patients treated. Angioplasty damages the arterial wall, with endothelial denudation and intimal and medial splitting. Why does this, and plaque injury, by stimulating platelet deposition, not produce more restenosis? Changes in arterial anatomy are likely to be important: the increase in vessel diameter and in blood flow produce conditions less favorable for thrombotic or arteriosclerotic restenosis.
现在有大量证据表明，早期病变形成和后期病变发展的某些方面是对损伤的一种反应。血流动力学因素在确定损伤部位方面很重要，并且可能直接造成损伤。在动物模型以及人类中，损伤均可导致动脉粥样硬化的形成。浅表损伤会使内皮下层暴露，从而使血小板发生黏附，在高剪切速率下，这种黏附依赖于血管性血友病因子（vWF）。血小板黏附和脱颗粒会释放血小板衍生生长因子（PDGF），后者会刺激平滑肌细胞增殖、合成功能以及血管收缩。在一些实验系统中，低密度脂蛋白（LDL）会刺激平滑肌细胞生长并损害内皮。因此，血小板和脂质在动脉粥样硬化中的作用之间建立了联系。血小板在动脉粥样硬化形成中作用的直接证据来自于一些研究，在这些研究中，对动物进行处理以减少血小板数量或功能，或者使血小板功能出现基因缺陷（患有血管性血友病的猪）。在这些模型中，血小板功能降低与动脉粥样硬化程度减轻相关。更深层的损伤会使胶原蛋白暴露，随后会发生血小板聚集、凝血酶和纤维蛋白生成。严重损伤后前列环素（PGI2）和纤溶因子产生减少的作用尚不清楚。血管的深层损伤发生在斑块破裂期间，这是大多数心肌梗死、不稳定型心绞痛以及一些猝死病例的病理过程。血管成形术可改善许多患者的症状，并且是安全的。然而，偶尔会发生急性闭塞，并且在接受治疗的患者中，约30%在第一年出现再狭窄。血管成形术会损害动脉壁，导致内皮剥脱以及内膜和中膜分离。为什么这样以及斑块损伤通过刺激血小板沉积却没有导致更多的再狭窄呢？动脉解剖结构的变化可能很重要：血管直径和血流的增加产生了不利于血栓形成或动脉硬化性再狭窄的条件。
