Randhawa Puneet Kaur, Jaggi Amteshwar Singh
Department of Pharmaceutical Sciences and Drug Research, Punjabi University Patiala, 147002, India.
Department of Pharmaceutical Sciences and Drug Research, Punjabi University Patiala, 147002, India.
Int J Cardiol. 2017 Feb 1;228:103-113. doi: 10.1016/j.ijcard.2016.11.205. Epub 2016 Nov 9.
Apart from modulating nociception, there is vital role of TRPV channels in modulating atherosclerosis, congestive heart failure, systemic hypertension, pulmonary hypertension, hemorrhagic shock and vascular remodeling. TRPV channel activation has shielding effect against the development of atherosclerosis and systemic hypertension. TRPV channel activation alleviates the formation of atherosclerotic lesions via increasing the expression of cholesterol efflux regulatory protein, UCP 2 and enhancing autophagy. Furthermore, activation of these channels enhances Na excretion and NO release to reduce the blood pressure. TRPV channel activation in the cardiac sensory neurons and subsequent CGRP release reduces ischemia-reperfusion injury. Activation of these channels during conditioning enhances CGRP and SP release from the sensory nerve fibers innervating the heart to induce cardioprotection. However, activation of these channels may elicit detrimental effects in pulmonary hypertension, hemorrhage and vascular remodeling. Activation of TRPV channels enhances smooth muscle cell proliferation to promote pulmonary hypertension. Moreover, TRPV channel inhibition reduces massive catecholamine release, improves survival during hemorrhage. Activation of these channels enhances vascular remodeling via enhancing NO release. Furthermore, dual role of TRPV channels has been reported in the perpetuation of congestive heart failure. On one hand, TRPV channel activation increases the expression of UCP2, PPAR- δ and mitochondrial sirtuin 3 to decrease oxidative stress and reduce heart injury. On the other hand, activation of these channels may enhance the expression of hypertrophic fibrotic proteins viz. GATA4, MMP to promote cardiac fibrosis. The present review discusses the dual role of activation of TRPV channels in diseases associated with cardiovascular system.
除了调节痛觉外，瞬时受体电位香草酸（TRPV）通道在调节动脉粥样硬化、充血性心力衰竭、系统性高血压、肺动脉高压、失血性休克和血管重塑中也起着至关重要的作用。TRPV通道激活对动脉粥样硬化和系统性高血压的发展具有保护作用。TRPV通道激活通过增加胆固醇流出调节蛋白、解偶联蛋白2（UCP 2）的表达并增强自噬来减轻动脉粥样硬化病变的形成。此外，这些通道的激活增强钠排泄和一氧化氮（NO）释放以降低血压。心脏感觉神经元中的TRPV通道激活及随后的降钙素基因相关肽（CGRP）释放可减轻缺血再灌注损伤。在预处理期间激活这些通道可增强支配心脏的感觉神经纤维释放CGRP和P物质（SP）以诱导心脏保护。然而，这些通道的激活在肺动脉高压、出血和血管重塑中可能引发有害影响。TRPV通道激活可增强平滑肌细胞增殖以促进肺动脉高压。此外，抑制TRPV通道可减少大量儿茶酚胺释放，提高出血期间的存活率。这些通道的激活通过增强NO释放来促进血管重塑。此外，TRPV通道在充血性心力衰竭的持续发展中具有双重作用。一方面，TRPV通道激活可增加UCP2、过氧化物酶体增殖物激活受体δ（PPAR-δ）和线粒体去乙酰化酶3（sirtuin 3）的表达，以降低氧化应激并减轻心脏损伤。另一方面，这些通道的激活可能增强肥厚性纤维化蛋白即GATA结合蛋白4（GATA4）、基质金属蛋白酶（MMP）的表达，以促进心脏纤维化。本综述讨论了TRPV通道激活在与心血管系统相关疾病中的双重作用。
