Fuster V, Badimon J J, Badimon L
Cardiac Unit, Massachusetts General Hospital, Harvard Medical School, Boston 02114.
Circulation. 1992 Dec;86(6 Suppl):III1-11.
The initiation of atherosclerosis may result from blood flow oscillatory shear stress in certain vascular sites (bending points, bifurcations, etc.) producing chronic minimal injury resulting in functional alteration of the arterial endothelium type I injury; experimentally, this is potentiated by atherogenic risk factors such as hypercholesterolemia, hypertension, immunocomplexes, viral infections, and tobacco smoke. Such minimal injury leads to accumulation of lipid and monocytes (macrophages), and subsequently, toxic products released by the macrophages produce damage of the intimal surface with denuding endothelium type II injury or damage, which attracts platelets; all of these cells release growth factors, prompting migration and proliferation of smooth muscle cells and producing a "fibro-intimal lesion" or the outside of the capsule of a predominant "lipid lesion." The lipid lesions surrounded by a thin capsule tend to be small and rupture easily, causing type III injury or damage; that is, they are soft and weak, contain large numbers of macrophages, which may release collagenase and elastase to form abscesses, and by their location, are under the effect of flow shear forces. After plaque disruption there is thrombus formation; when thrombi are small, they can become organized and contribute to the growth of the atherosclerotic plaque; when thrombi are large and occlusive, they lead to the acute coronary syndromes. New data suggest that, at the time of plaque disruption, certain "thrombogenic" risk factors modulate the degree of thrombogenicity and, thereby, the growth of the plaque versus the various acute coronary syndromes. Aside from the need for better understanding of the basic biology of atherogenesis, emphasis on identifying and modifying the primary atherogenic and thrombogenic risk factors should continue for primary prevention. Also, new approaches should focus on the identification, stabilization, and regression of the small "lipid plaques" prone to rupture (these are not necessarily angiographically apparent), as well as on the use of better and safer antithrombotic agents for prevention of progression.
动脉粥样硬化的起始可能源于某些血管部位（弯曲点、分叉处等）的血流振荡剪切应力，产生慢性微小损伤，导致动脉内皮I型损伤的功能改变；在实验中，高胆固醇血症、高血压、免疫复合物、病毒感染和烟草烟雾等致动脉粥样硬化危险因素会增强这种损伤。这种微小损伤会导致脂质和单核细胞（巨噬细胞）积聚，随后巨噬细胞释放的毒性产物会造成内膜表面损伤，出现内皮剥脱的II型损伤或损害，进而吸引血小板；所有这些细胞都会释放生长因子，促使平滑肌细胞迁移和增殖，形成“纤维内膜病变”或主要“脂质病变”包膜的外侧。被薄包膜包围的脂质病变往往较小且容易破裂，导致III型损伤或损害；也就是说，它们质地柔软且脆弱，含有大量巨噬细胞，巨噬细胞可能释放胶原酶和弹性蛋白酶形成脓肿，并且由于其位置，会受到血流剪切力的影响。斑块破裂后会形成血栓；当血栓较小时，它们可以机化并促进动脉粥样硬化斑块的生长；当血栓较大并阻塞血管时，会导致急性冠状动脉综合征。新数据表明，在斑块破裂时，某些“促血栓形成”危险因素会调节血栓形成程度，从而影响斑块生长与各种急性冠状动脉综合征的关系。除了需要更好地理解动脉粥样硬化发生的基本生物学机制外，对于一级预防，应继续强调识别和改变主要的动脉粥样硬化和促血栓形成危险因素。此外，新方法应侧重于识别、稳定和消退易于破裂的小“脂质斑块”（这些斑块不一定在血管造影中显影），以及使用更好、更安全的抗血栓药物来预防病情进展。
