Fisher M
Department of Neurology, Medical Center of Central Massachusetts, Worcester 01605.
Cerebrovasc Brain Metab Rev. 1991 Summer;3(2):114-33.
The pathogenesis of atherosclerosis has been extensively studied and the cellular aspects increasingly characterized. This review will focus on the basic pathology, presumed cellular events, cellular interactions, cell-lipid relationships, and potential therapies of atherosclerosis. Fatty streaks, fibrous plaques, and complicated plaques are the pathologic hallmarks of atherosclerosis. These lesions insidiously progress, and symptoms appear to develop when the plaque luminal surface destabilizes. The major cellular contributors to plaque development are monocytes/macrophages, endothelial cells, smooth muscle cells, and, to a lesser degree, lymphocytes and platelets. They interact in a complicated fashion. Growth factors and cytokines produced by these cells are also of great importance for cell-cell interaction. Hemodynamic factors contribute to atherogenesis at preferential sites within the arterial vasculature, presumably by effects on the cellular mechanisms. Hyperlipidemia, especially elevations of total and LDL-cholesterol, has been well characterized as an atherosclerotic risk factor. Cellular modification of LDL-cholesterol, primarily by oxidation, leads to more rapid uptake by macrophage-derived foam cells, enhancing plaque growth by this and other mechanisms. These observations may unify the cellular and lipid contributors to atherogenesis. Therapies directed at the cellular contributors to atherosclerosis are being assessed. Dietary n-3 fatty acid supplementation reduces the extent of experimental atherosclerosis, and human studies are in progress. Many potential cellular effects of n-3 fatty acids have been demonstrated. Other potential therapies for atherosclerosis that probably work at the cellular level include calcium channel blockers, antioxidants, and heparinoids. An exciting new era of atherosclerosis research and, hopefully, therapy has dawned, as knowledge about its cellular basis accrues.
动脉粥样硬化的发病机制已得到广泛研究，其细胞层面的特征也日益明确。本综述将聚焦于动脉粥样硬化的基本病理学、推测的细胞事件、细胞间相互作用、细胞与脂质的关系以及潜在治疗方法。脂肪条纹、纤维斑块和复杂斑块是动脉粥样硬化的病理标志。这些病变悄然进展，当斑块管腔表面不稳定时症状似乎才会出现。斑块形成的主要细胞成分是单核细胞/巨噬细胞、内皮细胞、平滑肌细胞，以及程度较轻的淋巴细胞和血小板。它们以复杂的方式相互作用。这些细胞产生的生长因子和细胞因子对细胞间相互作用也非常重要。血流动力学因素可能通过影响细胞机制，在动脉血管系统的特定部位促进动脉粥样硬化的发生。高脂血症，尤其是总胆固醇和低密度脂蛋白胆固醇升高，已被明确为动脉粥样硬化的危险因素。低密度脂蛋白胆固醇的细胞修饰，主要是通过氧化，导致巨噬细胞衍生的泡沫细胞更快摄取，通过这种及其他机制促进斑块生长。这些观察结果可能将细胞和脂质因素统一起来解释动脉粥样硬化的发生。针对动脉粥样硬化细胞成分的治疗方法正在评估中。膳食补充n-3脂肪酸可减轻实验性动脉粥样硬化的程度，相关人体研究正在进行。n-3脂肪酸的许多潜在细胞效应已得到证实。其他可能在细胞水平起作用的动脉粥样硬化潜在治疗方法包括钙通道阻滞剂、抗氧化剂和类肝素。随着对动脉粥样硬化细胞基础的认识不断积累，一个激动人心的动脉粥样硬化研究新时代，有望也是治疗新时代，已经到来。
