Activation of TRPV1 attenuates high salt-induced cardiac hypertrophy through improvement of mitochondrial function
Activation of TRPV1 attenuates high salt-induced cardiac hypertrophy through improvement of mitochondrial function
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TRPV1 的激活通过改善线粒体功能减轻高盐诱导的心脏肥大
DOI：
10.1111/bph.12987
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发表时间：
2015-12-01
影响因子：
7.3
通讯作者：
Zhu, Zhiming
中科院分区：
文献类型：
--
作者：
Lang, Hongmei;Li, Qiang;Zhu, Zhiming
背景与目的高盐饮食诱导心脏重构并导致心力衰竭，与心肌线粒体功能障碍密切相关。瞬时受体电位（TRP）通道参与心功能不全的发病机制。我们调查是否激活TRP香草酸（亚型1）（TRPV 1）通道饮食辣椒素可以，通过改善心脏线粒体功能障碍，防止高盐饮食诱导的心肌hypertrophy.Experimental ApproachMale野生型（WT）和TRPV 1（-/-）小鼠喂养正常或高盐饮食或无辣椒素6个月。测定心脏参数和耐力。线粒体呼吸和耗氧量测定采用高分辨率呼吸仪。TRPV 1，sirtuin 3和NDUFA 9的表达水平在心脏细胞和tissues.Key ResultsChronic高盐饮食引起的心脏肥大和减少体力活动的小鼠，这两种效果得到改善辣椒素摄入量在WT，但不是在TRPV 1（-/-）小鼠。TRPV 1敲除或高盐饮食显著危害线粒体复合物I氧化磷酸化（OXPHOS）的能力并降低复合物I酶活性。慢性饮食辣椒素以TRPV 1依赖性方式增加心脏线粒体sirtuin 3表达、复合体I OXPHOS活性、ATP产生和复合体I酶活性。结论和含义饮食辣椒素激活TRPV 1可以通过改善其对复合体I OXPHOS活性的有害影响来对抗高盐饮食介导的心脏损伤。TRPV 1介导的线粒体功能障碍的修正可能是早期心功能不全管理的新靶点。Linked Articles这篇文章是中国心血管药物发现创新主题部分的一部分。要查看本节中的其他文章，请访问http：//dx。doi。org/10.1111/bph。2015.172.问题-23
Background and PurposeHigh-salt diet induces cardiac remodelling and leads to heart failure, which is closely related to cardiac mitochondrial dysfunction. Transient receptor potential (TRP) channels are implicated in the pathogenesis of cardiac dysfunction. We investigated whether activation of TRP vanilloid (subtype 1) (TRPV1) channels by dietary capsaicin can, by ameliorating cardiac mitochondrial dysfunction, prevent high-salt diet-induced cardiac hypertrophy.Experimental ApproachMale wild-type (WT) and TRPV1(-/-) mice were fed a normal or high-salt diet with or without capsaicin for 6 months. Their cardiac parameters and endurance capacity were assessed. Mitochondrial respiration and oxygen consumption were measured using high-resolution respirometry. The expression levels of TRPV1, sirtuin 3 and NDUFA9 were detected in cardiac cells and tissues.Key ResultsChronic high-salt diet caused cardiac hypertrophy and reduced physical activity in mice; both effects were ameliorated by capsaicin intake in WT but not in TRPV1(-/-) mice. TRPV1 knockout or high-salt diet significantly jeopardized the proficiency of mitochondrial Complex I oxidative phosphorylation (OXPHOS) and reduced Complex I enzyme activity. Chronic dietary capsaicin increased cardiac mitochondrial sirtuin 3 expression, the proficiency of Complex I OXPHOS, ATP production and Complex I enzyme activity in a TRPV1-dependent manner.Conclusions and ImplicationsTRPV1 activation by dietary capsaicin can antagonize high-salt diet-mediated cardiac lesions by ameliorating its deleterious effect on the proficiency of Complex I OXPHOS. TRPV1-mediated amendment of mitochondrial dysfunction may represent a novel target for management of early cardiac dysfunction.Linked ArticlesThis article is part of a themed section on Chinese Innovation in Cardiovascular Drug Discovery. To view the other articles in this section visit http://dx. doi. org/10.1111/bph. 2015.172. issue-23