Relaxation of rat thoracic aorta by fibrate drugs correlates with their potency to disturb intracellular calcium of VSMCs
Relaxation of rat thoracic aorta by fibrate drugs correlates with their potency to disturb intracellular calcium of VSMCs
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贝特类药物对大鼠胸主动脉的舒张作用与其干扰 VSMC 细胞内钙的能力相关
DOI：
10.1016/j.vph.2012.01.003
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发表时间：
2012-03-01
影响因子：
4
通讯作者：
Dai, Renke
中科院分区：
文献类型：
--
作者：
Liu, Aiming;Yang, Julin;Dai, Renke
血管平滑肌细胞（VSMC）的表型修饰导致动脉粥样硬化的病理变化，其中细胞内钙的调节起着重要作用。在这项研究中，三种贝特类药物，即吉非贝齐 (Gem)、非诺贝酸 (Fa) 和苯扎贝特 (Beza)，被发现可以松弛胸主动脉，并降低培养的 VSMC 中细胞内钙 ([Ca2+](i)) 的效力。在预收缩的大鼠主动脉环上测定了 Gem、Fa 和 Beza 的松弛作用。添加这些贝特类药物后，通过激光扫描共聚焦显微镜或流式细胞术测量 VSMC 中的 [Ca2+](i) 水平。结果，三种贝特类药物显示出血管舒张活性，效力顺序为 Gem > Fa > Beza。使用 Gem 50 mg/L 观察到 [Ca2+](i) 持续有效减少，使用 Fa 400-600 mg/L 轻微减少，而在我们当前的系统下未检测到 Beza 的影响。因此，这些贝特类药物放松主动脉环的功效与其对 [Ca2+](i) 减少的影响密切相关，强烈暗示了潜在的因果关系。考虑到 Gem 在其临床浓度范围内有效降低 [Ca2+](i)，本研究建议深入了解抗动脉粥样硬化的原位药理作用和临床毒性风险。 (C) 2012 Elsevier Inc. 保留所有权利。
Phenotypic modifications of vascular smooth muscle cells (VSMCs) contribute to pathological changes in atherosclerosis where modulation of intracellular calcium plays an important role. In this study, three fibrate drugs, namely gemfibrozil (Gem), fenofibric acid (Fa) and bezafibrate (Beza), were revealed to relax thoracic aorta associated with their potency to reduce intracellular calcium ([Ca2+](i)) in cultured VSMCs. Relaxation effect of Gem, Fa and Beza was assayed on precontracted rat aortic rings. [Ca2+](i) level in VSMCs following addition of these fibrates was measured by laser scanning confocal microscopy or flow cytometry. Resultantly, three fibrates showed activity for vasodilation with potency order of Gem > Fa > Beza. Sustained potent reduction of [Ca2+](i) was observed with Gem 50 mg/L and mild reduction with Fa 400-600 mg/L, while no effect had been detected for Beza under our current system. Thus, the potency of these fibrates to relax aortic rings correlate well with their effect on [Ca2+](i) reduction, strongly implicating an underlying causal relationship. Considering that Gem potently reduces [Ca2+](i) in its clinical concentration range, this study suggests an insight to in situ pharmacological effects of anti-atherosclerosis and clinical toxicity risk. (C) 2012 Elsevier Inc. All rights reserved.