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检测和定位人心脏中非选择性阳离子通道 TRPC6 的蛋白表达。

Protein detection and localization of the non-selective cation channel TRPC6 in the human heart.

机构信息

Institute of Anatomy and Cell Biology, Saarland University, Medical Campus, Homburg, Saar, Germany.

Institute of Anatomy and Cell Biology, Saarland University, Medical Campus, Homburg, Saar, Germany.

出版信息

Eur J Pharmacol. 2022 Jun 5;924:174972. doi: 10.1016/j.ejphar.2022.174972. Epub 2022 Apr 26.

DOI:10.1016/j.ejphar.2022.174972
PMID:35483666
Abstract

Due to longer lifespans in societies in industrialized countries, cardiovascular diseases are becoming increasingly important for medical research. It has already been shown that the cell membrane-bound, non-selective TRPC6 ion channel is important in the pathogenesis of heart diseases. Among other things, it is permeable to calcium ion, which plays a critical role in cardiac contraction and relaxation. The TRPC6 ion channel is a promising therapeutic target in the treatment of cardiovascular diseases. A deeper understanding of the physiological and pathophysiological role as well as the localization of TRPC6 in human cardiac tissue is the basis for new drug development. Although the TRPC6 channel has been detected in animal studies, at the mRNA level in humans, and sparse TRPC6 protein has been detected in humans, there are no systematic studies of TRPC6 protein detection in the human heart. For the first time, TRPC6 ion channel protein was detected histologically in human heart tissue from body donors in different structures, localizations, and histological layers - particularly in cardiomyocytes and intramuscular arterioles - by immunohistochemistry, just as TRPC6 expression has already been shown in animal models of the heart by other research groups. In the sense of the translational concept, this indicates a possible transferability of research results from animal models to humans.

摘要

由于工业化国家的人们寿命延长,心血管疾病在医学研究中变得越来越重要。已经表明,细胞膜结合的非选择性 TRPC6 离子通道在心脏病的发病机制中很重要。除其他外,它对钙离子是可渗透的,钙离子在心脏收缩和松弛中起着关键作用。TRPC6 离子通道是治疗心血管疾病的有前途的治疗靶点。深入了解 TRPC6 在人类心脏组织中的生理和病理生理作用以及定位是新药物开发的基础。尽管在动物研究中已经检测到 TRPC6 通道,在人类中在 mRNA 水平上检测到 TRPC6,并且在人类中稀疏地检测到 TRPC6 蛋白,但在人类心脏中没有对 TRPC6 蛋白检测进行系统研究。首次通过免疫组织化学技术在不同结构、定位和组织学层的人体供体心脏组织中检测到 TRPC6 离子通道蛋白 - 特别是在心肌细胞和肌内小动脉中 - 正如其他研究小组已经在心脏动物模型中显示的那样。从转化概念的角度来看,这表明可以将动物模型的研究结果转移到人类身上。

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TRPC6 is ubiquitously present in lymphatic tissues: A study using samples from body donors.瞬时受体电位阳离子通道亚家族C成员6在淋巴组织中广泛存在:一项使用尸体捐赠者样本的研究。
Med Int (Lond). 2024 Aug 2;4(6):62. doi: 10.3892/mi.2024.186. eCollection 2024 Nov-Dec.
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Elderly with Varying Extents of Cardiac Disease Show Interindividual Fluctuating Myocardial TRPC6-Immunoreactivity.患有不同程度心脏病的老年人表现出个体间心肌瞬时受体电位通道6免疫反应性的波动。
J Cardiovasc Dev Dis. 2023 Jan 9;10(1):26. doi: 10.3390/jcdd10010026.