Bile acids regulate cardiovascular function.
Bile acids regulate cardiovascular function.
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DOI：
10.1111/j.1752-8062.2011.00272.x
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发表时间：
2011-06
期刊：
影响因子：
--
通讯作者：
Pallone TL
中科院分区：
文献类型：
--
作者：
Khurana S;Raufman JP;Pallone TL
过去十年的研究已经发现胆汁酸（BA）的作用超出了其调节脂质消化和胆固醇代谢的传统功能。BA现在被认为是与质膜和核受体相互作用的信号分子。新出现的证据表明，通过与这些受体相互作用，BA调节自身的合成，葡萄糖和能量稳态，以及其他重要的生理事件。在此，我们提供了一个全面的审查行动的BA对心血管功能。在心脏和体循环中，BA与质膜G蛋白偶联受体（例如TGR 5和毒蕈碱受体）和核受体（例如法尼醇（FXR）和异生素（PXR）受体）相互作用。BA受体在心血管组织中表达，然而，BA介导的心血管功能调节的机制仍然知之甚少。BA通过调节窦房和心室心肌细胞中的通道电导和钙动力学来降低心率，并通过内皮依赖性和非依赖性机制来调节血管张力。终末期肝病、梗阻性黄疸和妊娠期肝内胆汁淤积症是血清BA升高改变血管动力学的突出情况。本文综述了近年来发现的调节心血管功能的信号分子BA。
Research over the last decade has uncovered roles for bile acids (BAs) that extend beyond their traditional functions in regulating lipid digestion and cholesterol metabolism. BAs are now recognized as signaling molecules that interact with both plasma membrane and nuclear receptors. Emerging evidence indicates that by interacting with these receptors BAs regulate their own synthesis, glucose and energy homeostasis, and other important physiological events. Herein, we provide a comprehensive review of the actions of BAs on cardiovascular function. In the heart and the systemic circulation, BAs interact with plasma membrane G-protein coupled receptors, e.g. TGR5 and muscarinic receptors, and nuclear receptors, e.g. the farnesoid (FXR) and pregnane (PXR) xenobiotic receptors. BA receptors are expressed in cardiovascular tissue, however, the mechanisms underlying BA-mediated regulation of cardiovascular function remain poorly understood. BAs reduce heart rate by regulating channel conductance and calcium dynamics in sino-atrial and ventricular cardiomyocytes, and regulate vascular tone via both endothelium-dependent and -independent mechanisms. End-stage-liver disease, obstructive jaundice and intrahepatic cholestasis of pregnancy are prominent conditions in which elevated serum BAs alter vascular dynamics. This review focuses on BAs as newly-recognized signaling molecules that modulate cardiovascular function.
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