Anti-atherosclerotic potential of dihydropyridine calcium channel blockers.
Anti-atherosclerotic potential of dihydropyridine calcium channel blockers.
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DOI：
10.5551/jat.12450
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发表时间：
2012-09
影响因子：
4.4
通讯作者：
Norio Ishii;T. Matsumura;S. Shimoda;E. Araki
中科院分区：
文献类型：
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作者：
Norio Ishii;T. Matsumura;S. Shimoda;E. Araki
二氢吡啶类钙通道阻滞剂(CCBS)是高血压患者广泛使用的药物。二氢吡啶类CCBS主要通过扩张血管和降低外周阻力来降低血压，多项临床研究表明，它们对心血管疾病患者有临床益处。此外，一些研究表明，二氢吡啶CCBS除了具有降血压作用外，还具有抗动脉粥样硬化的作用。事实上，几项使用动脉粥样硬化模型动物的研究表明，二氢吡啶CCBS可以抑制动脉粥样硬化病变的形成。众所周知，活性氧(ROS)的产生通过刺激趋化因子、细胞因子和黏附分子等炎症因子的产生参与动脉粥样硬化的进展。二氢吡啶CCBS可以抑制血管细胞和动脉壁中ROS的产生和随后的炎症反应。此外，一些报道显示二氢吡啶CCBS抑制黏附分子的表达，从而抑制单核细胞与内皮细胞的黏附，这被认为是动脉粥样硬化发病的早期步骤。在血管细胞中，二氢吡啶CCBS在体外和体内都能抑制细胞的增殖和迁移。在巨噬细胞中，二氢吡啶CCBS减少胆固醇积聚和细胞内胆固醇酯化，并增加胆固醇酯水解率。此外，二氢吡啶CCBS抑制基质金属蛋白酶的表达，从而影响动脉粥样硬化斑块的稳定性。有趣的是，最近的研究表明，二氢吡啶CCBS的抗动脉粥样硬化作用至少部分是通过激活过氧化物酶体增殖物激活的受体γ来实现的。在这篇综述中，我们重点介绍二氢吡啶类CCBS的降压作用以外的抗动脉粥样硬化作用。
Dihydropyridine calcium channel blockers (CCBs) are widely used agents for patients with hypertension. Dihydropyridine CCBs lower blood pressure mainly through vasodilation and reduction of peripheral resistance, and several clinical studies have demonstrated that they have clinical benefits in patients with cardiovascular diseases. In addition, some studies have indicated that dihydropyridine CCBs have anti-atherogenic effects beyond their blood pressure-lowering effects. In fact, several studies using atherosclerotic model animals have revealed that dihydropyridine CCBs suppress atherosclerotic lesion formation. It is well known that the production of reactive oxygen species (ROS) is involved in the progression of atherosclerosis by stimulating the production of inflammatory factors such as chemokines, cytokines and adhesion molecules. Dihydropyridine CCBs can suppress ROS generation and subsequent inflammatory actions in vascular cells and arterial walls. Furthermore, several reports have revealed that dihydropyridine CCBs suppress the expression of adhesion molecules, thereby inhibiting monocyte adhesion to endothelial cells, which is thought to be an early step in the pathogenesis of atherosclerosis. In smooth muscle cells, dihydropyridine CCBs suppress cell proliferation and migration in vitro and in vivo. In macrophages, dihydropyridine CCBs decrease cholesterol accumulation and intracellular cholesterol esterification, and increase cholesteryl ester hydrolysis. Moreover, dihydropyridine CCBs suppress the expression of matrix metalloproteinases, which affects the stability of atheromatous plaques. Interestingly, recent studies have revealed that the anti-atherosclerotic effects of dihydropyridine CCBs are mediated, at least in part, via the activation of peroxisome proliferator-activated receptor-γ. In this review, we focus on the anti-atherosclerotic effects of dihydropyridine CCBs beyond their blood pressure-lowering effects.