The smooth muscle cell membrane during atherogenesis: a potential target for amlodipine in atheroprotection.
The smooth muscle cell membrane during atherogenesis: a potential target for amlodipine in atheroprotection.
复制标题
动脉粥样硬化形成过程中的平滑肌细胞膜：氨氯地平预防动脉粥样硬化的潜在靶点。
DOI：
10.1067/mhj.2001.109947
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发表时间：
2001
影响因子：
4.8
通讯作者：
Ferdinand,FD
中科院分区：
文献类型：
--
作者：
Tulenko,TN;Sumner,AE;Chen,M;Huang,Y;Laury-Kleintop,L;Ferdinand,FD
背景 动脉粥样硬化疾病显然从一开始就存在于人类群体中。然而，直到20世纪，传染病控制的进步才使得平均寿命延长到动脉粥样硬化能够影响普通人群的程度。到20世纪中叶，动脉粥样硬化已达到流行病水平，目前在世界范围内呈流行趋势并呈上升趋势。尽管它对医疗保健的重要性日益增加，但我们对血管壁斑块发生的细胞基础仍然知之甚少。目前的观点认为，动脉粥样硬化是由不受控制的慢性炎症过程引起的，该过程涉及动脉壁细胞及其与低密度脂蛋白和各种炎症细胞的相互作用。大量证据表明，动脉粥样硬化形成的主要损害是血清血脂异常和主要由氧化低密度脂蛋白介导的氧化应激。然而，这些损伤如何改变血管细胞的细胞生物学并导致动脉粥样硬化表型仍在深入研究中。此外，最近的临床试验提供的证据表明，某些类别的药物，包括新型钙通道阻滞剂（CCB），可以重塑动脉平滑肌细胞（SMC）膜并抑制动脉粥样硬化疾病的进展。方法这篇综述总结了我们目前对动脉 SMC 动脉粥样硬化形成的看法，并考虑了动脉粥样硬化形成早期 SMC 膜变化的最新进展。我们还讨论了某些 CCB 如何发挥作用来产生动脉粥样硬化保护。结果 血清高胆固醇血症发生后不久，SMC 膜就富含未酯化胆固醇。当膜胆固醇过多时，膜会变得更厚并形成独特的胆固醇域。这些膜的改变增加了 SMC 对钙的渗透性，并诱导 SMC 功能的各种改变，从而导致斑块形成过程中的细胞动脉粥样硬化过程。氨氯地平是第三代CCB，可显着抑制病变进展。这种新作用的解释可能在于该药物对各种潜在细胞靶标的影响。结论 越来越多的证据表明，过量的膜胆固醇可能导致细胞缺陷，从而导致 SMC 向动脉粥样硬化表型的转变。氨氯地平具有膜重塑特性，正在成为一种重要的动脉粥样硬化药物。 （Am Heart J 2001；141：S1-11。）
Background Atherosclerotic disease has been present in the human population apparently from the beginning of time. However, it has only been in the 20th century that improvements in the control of infectious diseases have allowed the average life span to increase to the point where atherosclerosis has been able to affect the general population. By the middle of the 20th century, atherosclerosis had reached epidemic levels, and it is currently pandemic and increasing worldwide. Despite its growing significance to health care, we still know relatively little about the cellular basis for plaque genesis in the vessel wall. Current thinking holds that atherosclerosis is caused by an unchecked chronic inflammatory process involving the cells of the arterial wall and their interaction with LDL and various inflammatory cells. Considerable evidence suggests that the principal insults underlying atherogenesis are serum dyslipidemias and oxidative stress mediated primarily by oxidized LDL. However, just how these insults alter the cell biology of vascular cells and lead to the atherosclerotic phenotype is still under intense investigation. Moreover, recent clinical trials have provided evidence that certain classes of drugs, including newer calcium channel blockers (CCBs), can remodel the arterial smooth muscle cell (SMC) membrane and inhibit the progression of atherosclerotic disease. Methods This review summarizes our current thinking on atherogenesis in the arterial SMC and considers recent developments regarding alterations in the SMC membrane during the very early period of atherogenesis. We also discuss how certain CCBs might operate to produce atheroprotection. Results The SMC membrane becomes enriched in unesterified cholesterol soon after the development of serum hypercholesterolemia. With excess membrane cholesterol, the membrane becomes thicker and develops distinct cholesterol domains. These alterations in the membrane increase the permeability of SMC to calcium and induce a variety of alterations in SMC function that contribute to cellular atherogenic processes during plaque genesis. Amlodipine, a third-generation CCB, markedly inhibits the progression of lesions. The explanation of this novel action may lie in the effects of this drug on various potential cellular targets. Conclusions Evidence is accumulating that excess membrane cholesterol may contribute to the cellular defects responsible for the transformation of the SMC to the atherosclerotic phenotype. Amlodipine, which has membrane–remodeling properties, is emerging as an important atheroprotective drug. (Am Heart J 2001;141:S1-11.)