RyR2基因突变所致CPVT的研究进展

刁小川; 李健; 郑娜

doi:10.13201/j.issn.1001-1439.2018.04.023

RyR2基因突变所致CPVT的研究进展

- 1 哈尔滨医科大学第一临床医学院(哈尔滨, 150000);
- 2 南京市公安局浦口分局;
- 3 深圳大学医学部基础医学院病理学教研室

详细信息

通讯作者: 郑娜,E-mail:zhengna@szu.edu.cn

中图分类号: R541.7

收稿日期: 2017-11-01

Research advances in CPVT caused by the gene mutation of RyR2

- 1 The First Affiliated Hospital of Harbin Medical University, Haerbin, 150000, China;
- 2 Pukou Branch of Nanjing Municipal Public Security Bureau;
- 3 Department of Pathology, School of Medicine, Shenzhen University

More Information

Corresponding author: ZHENG Na, E-mail: zhengna@szu.edu.cn

Received Date: 01 November 2017

摘要

摘要: 作为一种罕见的遗传性疾病, 儿茶酚胺敏感性多形性室性心动过速 (catecholaminergic polymorphous ventricular tachycardia, CPVT) 被视为心源性猝死的重要原因之一。大量研究发现, Ryanodine受体2 (RyR2) 基因突变可以导致CPVT。RyR2是存在于心肌细胞肌浆网上的一种钙释放通道, 其调控异常、结构改变等均可导致心肌细胞自发性Ca²⁺泄漏, 引发多种心脏疾病, 严重时可出现心力衰竭, 甚至猝死。本文主要综述RyR2基因突变与CPVT的关系, 以及将RyR2作为靶点的CPVT临床治疗及法医学诊断价值。
- 儿茶酚胺敏感性多形性室性心动过速 /
- Ryanodine受体2 /
- 基因突变
Abstract: As a rare hereditary disease, catecholaminergic polymorphous ventricular tachycardia (CPVT) is considered as a major cause of sudden unexpected cardiac death.Amount of research have reveal that the gene mutations of Ryanodine receptor 2 (RyR2) was recognized as a part of the pathophysiology of CPVT.The RyR2, a Ca²⁺release channel on the sarcoplasmic reticulum, plays a key role in the event of spontaneous Ca²⁺leakage and sequential cardiac disease, even heart failure and sudden cardiac death, which was mainly due to the abnormal regulation and structural modifications of RyR2.In the present article, we present an overview of the advances in the gene mutations of RyR2 in CPVT and discuss the implications of the findings for CPVT therapy and forensic diagnosis.
- catecholaminergic polymorphous ventricular tachycardia /
- Ryanodine receptor 2 /
- Gene mutation

HTML全文

参考文献(17)

[1]	Fearnley CJ, Roderick HL, Bootman MD.Calcium signaling in cardiac myocytes[J].Cold Spring Harb Perspect Biol, 2011, 3 (11):a004242.
[2]	Amador FJ, Stathopulos PB, Enomoto M, et al.Ryanodine receptor calcium release channels:lessons from structure-function studies[J].FEBS J, 2013, 280 (21):5456-5470.
[3]	Zhao YT, Guo YB, Gu L, et al.Sensitized signaling between L-type Ca²⁺ channels and ryanodine receptors in the absence or inhibition of FKBP 12.6 in cardiomyocytes[J].Cardiovasc Res, 2017, 113 (3):332-342.
[4]	O'Brien F, Venturi E, Sitsapesan R.The ryanodine receptor provides high throughput Ca²⁺ -release but is precisely regulated by networks of associated proteins:a focus on proteins relevant to phosphorylation[J].Biochem Soc Trans, 2015, 43 (3):426-433.
[5]	Bovo E, Huke S, Blatter LA, et al.The effect of PKA-mediated phosphorylation of pyanodine receptor on SR Ca²⁺ leak in ventricular myocytes[J].J Mol Cell Cardiol, 2017, 104:9-16.
[6]	Bobin P, Varin A, Lefebvre F, et al.Calmodulin kinaseⅡinhibition limits the pro-arrhythmic Ca²⁺ waves induced by cAMP-phosphodiesterase inhibitors[J].Cardiovasc Res, 2016, 110 (1):151-161.
[7]	Kushnir A, Marks AR.The ryanodine receptor in cardiac physiology and disease[J].Adv Pharmacol, 2010, 59:1-30.
[8]	Handhle A, Ormonde CE, Thomas NL, et al.Clasequestrin interacts directly with the cardiac ryanodine receptor luminal domain[J].J Cell Sci, 2016, 129 (21):3983-3988.
[9]	郭继鸿.原发遗传性心律失常的诊治精要[J].临床心血管病杂志, 2015, 31 (11):1141-1146.
[10]	Venetucci L, Denegri M, Napolitano C, et al.Inherited calcium channelopathies in the pathophysiology of arrhythmias[J].Nat Rev Cardiol, 2012, 9 (10):561-571.
[11]	Priori SG, Chen SR.Inherited dysfunction of sarcopiasmic reticulum Ca²⁺ handling and arrhythmogenesis[J].Circ Res, 2011, 108 (7):871-883.
[12]	Zhao YT, Valdivia CR, Gurrola GB, et al.Arrhythmogenic mechanisms in ryanodine receptor channelopathies[J].Sci China Life Sci, 2015, 58 (1):54-58.
[13]	Priori SG, Napolitano C.Cardiac and skeletal muscle disorders caused by mutations in the intracellular Ca^ (2+) release channels[J].J Clin Invest, 2005, 115 (8):2033-2038.
[14]	Meli AC, Refaat MM, Dura M, et al.A novel ryanodine receptor mutation linked to sudden death increases sensitivity to cytosolic calcium[J].Circ Res, 2011, 109 (3):281-290.
[15]	Leren IS, Saberniak J, Majid E, et al.Nadolol decreases the incidence and severity of ventricular arrhythmias during exercise stress testing compared with beta1-selective beta-blockers in patients with catecholaminergic polymorphic ventricular tachycardia[J].Heart Rhythm, 2016, 13 (2):433-440.
[16]	Bannister ML, Thomas NL, Sikkel MB, et al.The mechanism of flecainide action in CPVT does not involve a direct effect on RyR2[J].Circ Res, 2015, 116 (8):1324-1335.
[17]	Thevis M, Schänzer W.Analytical approaches for the detection of emerging therapeutics and non-approved drugs in human doping controls[J].J Pham Biomed Anal, 2014, 101:66-83.