Department of Cardiology, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan; Support Center for Women Health Care Professionals and Researchers, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan.
Department of Anatomy and Neurobiology, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan.
Life Sci. 2015 May 15;129:27-34. doi: 10.1016/j.lfs.2014.10.022. Epub 2014 Nov 12.
Epigenetic factors of pressure load, fluid force, and electrical fields that occur during cardiac contraction affect cardiac development, morphology, function, and pathogenesis. These factors are orchestrated by intercellular communication mediated by gap junctions, which synchronize action potentials and second messengers. Misregulation of the gap junction protein connexin (Cx) alters cardiogenesis, and can be a pathogenic factor causing cardiac conduction disturbance, fatal arrhythmia, and cardiac remodeling in disease states such as hypertension and ischemia. Changes in Cx expression can occur even when the DNA sequence of the Cx gene itself is unaltered. Posttranslational modifications might reduce arrhythmogenic substrates, improve cardiac function, and promote remodeling in a diseased heart. In this review, we discuss the epigenetic features of gap junctions that regulate cardiac morphology and remodeling. We further discuss potential clinical applications of current knowledge of the structure and function of gap junctions.
心脏收缩过程中产生的压力负荷、流体力和电场等表观遗传因素会影响心脏发育、形态、功能和发病机制。这些因素由间隙连接介导的细胞间通讯来协调，从而同步动作电位和第二信使。间隙连接蛋白连接子（Cx）的调控失常会改变心脏发生，并且可能成为导致心脏传导障碍、致命性心律失常和高血压和缺血等疾病状态下心脏重构的致病因素。即使 Cx 基因本身的 DNA 序列没有改变，Cx 表达的变化也可能发生。翻译后修饰可能会减少心律失常底物，改善心脏功能，并促进患病心脏的重塑。在这篇综述中，我们讨论了调节心脏形态和重塑的间隙连接的表观遗传特征。我们还进一步讨论了目前对间隙连接结构和功能的认识的潜在临床应用。
