主页 > 医药科学 >
【medical-news】科学家揭示心房颤动新调控机理
作者：杨宝峰等 来源：《循环》
由哈尔滨医科大学“重大心脏疾病基础研究”973项目首席科学家杨宝峰院士领衔的科研团队，于近期在国际上首次发现临床最为常见的心律失常类型——心房颤动发生的新机理及微小核苷酸-328调控心房颤动的发生。这一发现于日前发表在国际心血管领域权威杂志《循环》上。
课题组发现心房颤动的患者微小核苷酸-328显著升高，且升高程度与发病程度密切相关。为揭开微小核苷酸-328在房颤中的“奥秘”，杨宝峰及课题组成员联手攻关，在国际上首次建立起心脏特定微小核苷酸(1，26，328亚型)过表达转基因鼠和微小核苷酸功能敲减小鼠(328亚型)，发现微小核苷酸-328的过表达能诱发出小鼠的心房颤动，而微小核苷酸-328功能敲减小鼠给予腺病毒转染的微小核苷酸-328反义寡核苷酸，则可减轻房颤的发生。
为进一步揭秘微小核苷酸-328升高诱发心房颤动的靶点，课题组运用多种实验证明，微小核苷酸-328使编码钙通道的两个基因CACNA1C和CACNB1蛋白表达，且L型钙电流大小也随之显著降低。相反，抑制微小核苷酸-328可减少房颤的发生。课题组通过大量离体、在体动物的实验和临床观察，最终确定微小核苷酸-328为心房颤动发生的关键调控分子，首次从微小核苷酸领域这一分子水平上解读心房颤动的发生机理，由此锁定了一个可以治疗房颤的新靶点，对心房颤动的诊治有着重大意义，为心脏疾病领域的生物医药产业的创新研发奠定了基础。（来源：科技日报 衣晓峰 陈英云 李丽云） 又是一个重大发现。 [来自丁香园WAP]
呵呵，中国的科学家好好那努力哈！ 美丽的母校-哈尔滨医科大学-的校长！ 为我们有这样的校长自豪，向校长学习！ 团队凝心聚力的力量 哈医大出人才啊！怪不得哈工大合并不去。 为母校感到骄傲！ 呵呵！ 为母校有这样的校长骄傲！哈医大加油！ 顶一下 哈医大的骄傲，杨校长加油 哈医大的骄傲，杨校长加油。。。 校长大人啊。。哈哈好怀念的名字啊。在我的毕业证书上！说实话 杨校长长的很帅气！ 宝峰哥太崇拜你了~~不愧为我的偶像！！身为医大人 为医大骄傲！ 有原文吗？ 看来园子里很多校友哦 交流过一次，感觉杨校长不难接触。circulation不容易啊 顶！！！ 虽然有北协和南湘雅，
但是医大是我以前最崇拜的学校。 宝峰哥，厉害。再接再厉。 本科在哈医大上的，哈医大加油，校长加油 医大人，加油，，自己也要加油！ oh , we are so pround of you , mrt yang ,and thank you for your new foundings , which will help a lot of people who is suffering from atrial fibrilation . you build a good example for us , all harbin medical university doctors and students , give all my reapects to you , and i believe it encourage me a lot with my own experiment , thank you again . 这个课题做了很久了啊 为母校感到自豪！ 怀念母校！ 为母校自豪。为杨校长自豪！ 一将功成万骨枯 microRNA在心脏疾病中的作用已成为研究热点 为母校有这样的校长骄傲！哈医大加油！ 杨校长是搞药理的 卫生部统编教材的主编<<药理学>> 我们的杨校长 顶 顶 Circulation. 2010 Dec 7;122(23):2378-87. Epub 2010 Nov 22.
MicroRNA-328 Contributes to Adverse Electrical Remodeling in Atrial Fibrillation.
Lu Y, Zhang Y, Wang N, Pan Z, Gao X, Zhang F, Zhang Y, Shan H, Luo X, Bai Y, Sun L, Song W, Xu C, Wang Z, Yang B.
FAHA, Research Center, Montreal Heart Institute, 5000 Belanger E, Montreal, PQ H1T 1C8, QC, Canada.
Abstract
Background- A characteristic of both clinical and experimental atrial fibrillation (AF) is atrial electric remodeling associated with profound reduction of L-type Ca(2+) current and shortening of the action potential duration. The possibility that microRNAs (miRNAs) may be involved in this process has not been tested. Accordingly, we assessed the potential role of miRNAs in regulating experimental AF. Methods and Results- The miRNA transcriptome was analyzed by microarray and verified by real-time reverse-transcription polymerase chain reaction with left atrial samples from dogs with AF established by right atrial tachypacing for 8 weeks and from human atrial samples from AF patients with rheumatic heart disease. miR-223, miR-328, and miR-664 were found to be upregulated by >2 fold, whereas miR-101, miR-320, and miR-499 were downregulated by at least 50%. In particular, miR-328 level was elevated by 3.9-fold in AF dogs and 3.5-fold in AF patients relative to non-AF subjects. Computational prediction identified CACNA1C and CACNB1, which encode cardiac L-type Ca(2+) channel α1c- and β1 subunits, respectively, as potential targets for miR-328. Forced expression of miR-328 through adenovirus infection in canine atrium and transgenic approach in mice recapitulated the phenotypes of AF, exemplified by enhanced AF vulnerability, diminished L-type Ca(2+) current, and shortened atrial action potential duration. Normalization of miR-328 level with antagomiR reversed the conditions, and genetic knockdown of endogenous miR-328 dampened AF vulnerability. CACNA1C and CACNB1 as the cognate target genes for miR-328 were confirmed by Western blot and luciferase activity assay showing the reciprocal relationship between the levels of miR-328 and L-type Ca(2+) channel protein subunits. Conclusions- miR-328 contributes to the adverse atrial electric remodeling in AF through targeting L-type Ca(2+) channel genes. The study therefore uncovered a novel molecular mechanism for AF and indicated miR-328 as a potential therapeutic target for AF. 呵呵 全是校友啊！好好！顶下！ 山东大学文件类型:DOC/Microsoft Word- 文字版阐明蜕皮相关基因的表达调控机理,获得国家自然科学基金重点项目支持. 2002-2004年... 《心房颤动电重构和解剖重构》三项系列研究中全部子课题的研究.跟踪国际科技前沿的...www.subject.sdu.edu.cn/....doc-2010-12-25-山东大学文件类型:DOC/Microsoft Word- 文字版阐明蜕皮相关基因的表达调控机理,获得国家自然科学基金重点项目支持. 2002-2004年... 《心房颤动电重构和解剖重构》三项系列研究中全部子课题的研究.跟踪国际科技前沿的...www.subject.sdu.edu.cn/....doc-2010-12-23-[标签:content2]
阅读本文的人还阅读：
作者:admin@医学,生命科学 2011-01-04 00:42
医学,生命科学网