Beyond genomics-technological advances improving the molecular characterization and precision treatment of heart failure.
Beyond genomics-technological advances improving the molecular characterization and precision treatment of heart failure.
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超越基因组学：技术进步改善心力衰竭的分子特征和精确治疗。
DOI：
10.1007/s10741-020-10021-5
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发表时间：
2021-03
影响因子：
4.6
通讯作者：
Greenberg MJ
中科院分区：
文献类型：
--
作者：
Lavine KJ;Greenberg MJ
扩张型心肌病（DCM）是心力衰竭和心血管死亡的主要原因。在过去的 20 年里，人们极大地关注开发针对常见下游疾病途径的治疗方法，这些途径被认为与所有形式的心力衰竭有关，与最初的病因无关。虽然这种策略在人群水平上有效，但个体反应差异很大，只有大约三分之一的患者从现代心力衰竭治疗中受益。从这个角度来看，我们建议DCM应被视为具有左心室扩张和收缩功能障碍的常见表型的疾病的集合，而不是单一的疾病实体，并且基于机制的疾病亚型分类将彻底改变我们对DCM的理解和临床方法。我们讨论这些努力如何成为实现精准医学潜力的核心，以及如何通过新工具的开发来增强这些努力，使研究人员能够战略性地利用基因组和转录组信息。最后，我们概述了一项研究策略，1）在患者层面定义 DCM，2）开发新工具来建模和机械剖析人类心力衰竭的亚型，3）利用这些见解来开发精准治疗。
Dilated cardiomyopathy (DCM) is a major cause of heart failure and cardiovascular mortality. In the past 20 years, there has been an overwhelming focus on developing therapeutics that target common downstream disease pathways thought to be involved in all forms of heart failure independent of the initial etiology. While this strategy is effective at the population level, individual responses vary tremendously and only approximately one third of patients receive benefit from modern heart failure treatments. In this perspective, we propose that DCM should be considered as a collection of diseases with a common phenotype of left ventricular dilation and systolic dysfunction rather than a single disease entity, and that mechanism-based classification of disease subtypes will revolutionize our understanding and clinical approach towards DCM. We discuss how these efforts are central to realizing the potential of precision medicine and how they are empowered by the development of new tools that allow investigators to strategically employ genomic and transcriptomic information. Finally, we outline an investigational strategy to 1) define DCM at the patient level, 2) develop new tools to model and mechanistically dissect subtypes of human heart failure, and 3) harness these insights for the development of precision therapeutics.
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影响因子：
20.1
作者：
Feaster TK;Cadar AG;Wang L;Williams CH;Chun YW;Hempel JE;Bloodworth N;Merryman WD;Lim CC;Wu JC;Knollmann BC;Hong CC
通讯作者：
Hong CC
DOI：
10.1152/ajpheart.00571.2005
发表时间：
2005-11-01
影响因子：
4.8
作者：
Chandra, M;Tschirgi, ML;Tardiff, JC
通讯作者：
Tardiff, JC
影响因子：
5
作者：
Ford SJ;Mamidi R;Jimenez J;Tardiff JC;Chandra M
通讯作者：
Chandra M
影响因子：
4.8
作者：
Eschenhagen, T;Fink, C;Elson, EL
通讯作者：
Elson, EL
影响因子：
11.8
作者：
DeLaughter, Daniel M.;Bick, Alexander G.;Wakimoto, Hiroko;McKean, David;Gorham, Joshua M.;Kathiriya, Irian S.;Hinson, John T.;Homsy, Jason;Gray, Jesse;Pu, William;Bruneau, Benoit G.;Seidman, J. G.;Seidman, Christine E.
通讯作者：
Seidman, Christine E.