Cardiac myosin binding protein-C: a novel sarcomeric target for gene therapy.
Cardiac myosin binding protein-C: a novel sarcomeric target for gene therapy.
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DOI：
10.1007/s00424-013-1412-z
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发表时间：
2014-02
影响因子：
4.5
通讯作者：
Stelzer, Julian E.
中科院分区：
文献类型：
--
作者：
Mamidi, Ranganath;Li, Jiayang;Gresham, Kenneth S.;Stelzer, Julian E.
心肌肌球蛋白结合蛋白-C (cMyBP-C) 能够与肌节内的粗丝蛋白和细丝蛋白相互作用，从而调节心肌的收缩特性。人类遗传性肥厚型心肌病病例很大一部分是由 cMyBP-C 突变引起的，这一事实强调了 cMyBP-C 在心脏功能中的核心调节作用。 cMyBP-C 相关心肌病的主要功能障碍可能是肌丝收缩功能异常；然而，目前还没有有效的疗法来改善这些收缩缺陷。因此，迫切需要设计新的疗法来恢复 cMyBP-C 相关心肌病的正常收缩功能。为此，现在可以利用从各种结构、功能和生化研究中收集的概念来设计 cMyBP-C 蛋白，当将其纳入肌节时，可以显着改善收缩功能。在这篇综述中，我们讨论了基于 cMyBP-C 的基因疗法的基本原理，该疗法可用于治疗遗传性和获得性心肌病的收缩功能障碍。
Through its ability to interact with both the thick and thin filament proteins within the sarcomere, cardiac myosin binding protein-C (cMyBP-C) regulates the contractile properties of the myocardium. The central regulatory role of cMyBP-C in heart function is emphasized by the fact that a large proportion of inherited hypertrophic cardiomyopathy cases in humans are caused by mutations in cMyBP-C. The primary dysfunction in cMyBP-C-related cardiomyopathies is likely to be abnormal myofilament contractile function; however, currently, there are no effective therapies for ameliorating these contractile defects. Thus, there is a compelling need to design novel therapies to restore normal contractile function in cMyBP-C-related cardiomyopathies. To this end, concepts gleaned from various structural, functional, and biochemical studies can now be utilized to engineer cMyBP-C proteins that, when incorporated into the sarcomere, can significantly improve contractile function. In this review, we discuss the rationale for cMyBP-C-based gene therapies that can be utilized to treat contractile dysfunction in inherited and acquired cardiomyopathies.
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影响因子：
20.1
作者：
Harris SP;Lyons RG;Bezold KL
通讯作者：
Bezold KL
影响因子：
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作者：
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Roger VL;Go AS;Lloyd-Jones DM;Benjamin EJ;Berry JD;Borden WB;Bravata DM;Dai S;Ford ES;Fox CS;Fullerton HJ;Gillespie C;Hailpern SM;Heit JA;Howard VJ;Kissela BM;Kittner SJ;Lackland DT;Lichtman JH;Lisabeth LD;Makuc DM;Marcus GM;Marelli A;Matchar DB;Moy CS;Mozaffarian D;Mussolino ME;Nichol G;Paynter NP;Soliman EZ;Sorlie PD;Sotoodehnia N;Turan TN;Virani SS;Wong ND;Woo D;Turner MB;American Heart Association Statistics Committee and Stroke Statistics Subcommittee
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American Heart Association Statistics Committee and Stroke Statistics Subcommittee
影响因子：
37.8
作者：
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通讯作者：
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3.4
作者：
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通讯作者：
Maughan, David W.