Vascular KCa-channels as therapeutic targets in hypertension and restenosis disease.
Vascular KCa-channels as therapeutic targets in hypertension and restenosis disease.
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DOI：
10.1517/14728220903540257
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发表时间：
2010-02
影响因子：
5.8
通讯作者：
Wulff H
中科院分区：
文献类型：
--
作者：
Köhler R;Kaistha BP;Wulff H
血管Ca 2+激活的K+通道（KCa）是控制动脉张力的重要效应蛋白，并且已报道KCa通道功能的改变促成广泛的心血管病理。在动脉内皮中，KCa 3.1和KCa 2.3亚型的KCa通道被认为介导膜超极化，从而启动内皮源性超极化因子（EDHF）介导的血管扩张反应，这是仅次于一氧化氮和前列环素（PGI 2）的第三大内皮扩张系统。在各种心血管疾病状态下，如高血压、糖尿病、肾功能不全和血管成形术干预和旁路手术后的内皮功能障碍，内皮中KCa3.1和KCa2.3通道功能减弱被认为是导致血管调节缺陷的原因。此外，已显示KCa的上调驱动动脉平滑肌细胞的增殖，从而触发血管成形术和动脉粥样硬化后的再狭窄。本文综述了血管KCa3.1和KCa2.3通道的分子和药理学特性及其在心血管疾病中的作用。在这篇综述中，我们强调了KCa3.1/KCa2.3调节剂作为新型内皮特异性抗高血压药物的治疗潜力，以及KCa3.1阻滞剂治疗以细胞过度增殖为特征的心血管疾病的有用性。
Vascular Ca2+-activated K+ channels (KCa) are important effector proteins in the control of arterial tone and alterations in KCa channel functions have been reported to contribute to a wide range of cardiovascular pathologies. In the arterial endothelium KCa channels of the KCa3.1 and KCa2.3 subtypes have been proposed to mediate membrane hyperpolarisation and thus initiate the endothelium-derived hyperpolarizing factor (EDHF)-mediated vasodilator response, the third major endothelial dilator system next to nitric oxide and prostacyclin (PGI2). In a variety of cardiovascular disease states such as hypertension, diabetes, renal insufficiency, and endothelial dysfunction following angioplastic interventions and by-pass surgery, diminished functions of KCa3.1 and KCa2.3 channels in the endothelium have been proposed to contribute to defective vasoregulation. Moreover, up-regulation of KCa has been shown to drive proliferation of arterial smooth muscle cells and thus trigger restenosis after angioplasty and atherosclerosis. In this review, we summarize current knowledge about vascular KCa3.1 and KCa2.3 channels, their molecular and pharmacological properties and their specific roles in cardiovascular pathologies. In this review, we highlight the therapeutic potential of KCa3.1/KCa2.3 modulators as novel endothelial specific antihypertensive drugs as well as the usefulness of KCa3.1-blockers for treating cardiovascular diseases characterized by excessive cell proliferation.
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作者：
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DOI：
10.1152/ajpheart.00292.2006
发表时间：
2006-09-01
影响因子：
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作者：
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通讯作者：
Vanhoutte, Paul M.