Lüscher T F, Oemar B S, Yang Z, Noll G
Kardiologie und Kardiovaskuläre Forschung, Universitätsklinik Inselspital, Bern, Schweiz.
Z Kardiol. 1996 Jul;85(7):495-508.
Atherosclerosis and its consequences account for most of morbidity and mortality in Western countries. Atherosclerosis develops over a period of decades and has a complex pathogenesis. It is a disease of the intima and primarily involves four cell types, i.e., endothelial and vascular smooth muscle cells, monocytes and platelets. In recent years, knowledge on the cellular and molecular mechanisms of these cells and their alterations by cardiovascular risk factors and in atherosclerosis has greatly expanded. In particular, it became clear that endothelial cells play a crucial role in the regulation of platelet function, coagulation as well as vascular tone and structure. Interestingly, endothelial dysfunction occurs early, particularly if cardiovascular risk factors such as hyperlipidemia, hypertension and diabetes are present. This could lead to adhesion of circulating platelets and monocytes and increased accumulation of lipids in the subintima as well as increased contraction, migration and proliferation of vascular smooth muscle cells. The fact that atherosclerosis develops only in certain, but not in other parts of the circulation, however, has rarely been considered. With the development of molecular biology techniques it became possible to clone differentially expressed genes in vessels with or without atherosclerosis; this in turn allows to better characterize the molecular and cellular mechanisms of the disease. The search for such candidate genes could set the basis for future genetic interventions. This therapeutic approach is likely to reach clinical importance particularly in monogenetic diseases (i.e., familial hypercholesterinemia), while its use in complex polygenetic diseases such as atherosclerosis is more difficult. Restenosis, however, may be accessible to gene therapy earlier on as it is amenable to local gene transfection.
在西方国家，动脉粥样硬化及其后果是导致大部分发病和死亡的原因。动脉粥样硬化的发展历经数十年，其发病机制复杂。它是一种内膜疾病，主要涉及四种细胞类型，即内皮细胞、血管平滑肌细胞、单核细胞和血小板。近年来，关于这些细胞的细胞和分子机制以及它们如何受到心血管危险因素影响和在动脉粥样硬化中发生改变的知识有了极大的扩展。特别是，很明显内皮细胞在血小板功能、凝血以及血管张力和结构的调节中起着关键作用。有趣的是，内皮功能障碍很早就会出现，尤其是在存在高脂血症、高血压和糖尿病等心血管危险因素的情况下。这可能导致循环中的血小板和单核细胞黏附，内膜下脂质蓄积增加，以及血管平滑肌细胞收缩、迁移和增殖增加。然而，动脉粥样硬化仅在循环系统的某些特定部位而非其他部位发生这一事实却很少被考虑。随着分子生物学技术的发展，克隆有或没有动脉粥样硬化的血管中差异表达的基因成为可能；这反过来又有助于更好地描述该疾病的分子和细胞机制。寻找此类候选基因可为未来的基因干预奠定基础。这种治疗方法可能在单基因疾病（即家族性高胆固醇血症）中尤其具有临床重要性，而在动脉粥样硬化等复杂多基因疾病中的应用则更为困难。然而，再狭窄可能更早地适用于基因治疗，因为它适合局部基因转染。
