Cardiac T-Tubule cBIN1-Microdomain, a Diagnostic Marker and Therapeutic Target of Heart Failure.
Cardiac T-Tubule cBIN1-Microdomain, a Diagnostic Marker and Therapeutic Target of Heart Failure.
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DOI：
10.3390/ijms22052299
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发表时间：
2021-02-25
影响因子：
5.6
通讯作者：
Hong T
中科院分区：
文献类型：
--
作者：
Li J;Richmond B;Hong T
由于其首次被鉴定为心脏横小管（t-小管）蛋白，随后克隆了负责t-小管膜微区形成的心脏同种型，心脏桥接整合子1（cBIN 1）及其组织化微区已成为维持正常心跳心脏收缩和舒张的关键机制。cBIN 1-微结构域的异常重塑发生在应激和患病的心肌细胞中，有助于心力衰竭的病理生理学。由于t-小管cBIN 1-微结构域通过微泡释放到外周循环中的稳态周转，血浆cBIN 1可以作为心肌细胞健康的液体活检来测定。一种新的血液检测cBIN 1评分（CS）已被开发为从血浆cBIN 1浓度衍生的无量纲倒数指数，对射血分数降低或保留的心力衰竭（HFrEF或HFpEF）稳定的非卧床患者的临床结局具有诊断和预后能力。最近的证据进一步表明，通过基于腺相关病毒9的基因治疗引入的外源性cBIN 1可以挽救衰竭心脏的心脏收缩和舒张。cBIN 1基因治疗的治疗潜力是巨大的，因为它能够拯救心脏收缩力，同时提供Lustropic保护。cBIN 1基因治疗的这些前所未有的能力正在改变目前心力衰竭（特别是HFpEF）治疗开发的范式。
Since its first identification as a cardiac transverse tubule (t-tubule) protein, followed by the cloning of the cardiac isoform responsible for t-tubule membrane microdomain formation, cardiac bridging integrator 1 (cBIN1) and its organized microdomains have emerged as a key mechanism in maintaining normal beat-to-beat heart contraction and relaxation. The abnormal remodeling of cBIN1-microdomains occurs in stressed and diseased cardiomyocytes, contributing to the pathophysiology of heart failure. Due to the homeostatic turnover of t-tubule cBIN1-microdomains via microvesicle release into the peripheral circulation, plasma cBIN1 can be assayed as a liquid biopsy of cardiomyocyte health. A new blood test cBIN1 score (CS) has been developed as a dimensionless inverse index derived from plasma cBIN1 concentration with a diagnostic and prognostic power for clinical outcomes in stable ambulatory patients with heart failure with reduced or preserved ejection fraction (HFrEF or HFpEF). Recent evidence further indicates that exogenous cBIN1 introduced by adeno-associated virus 9-based gene therapy can rescue cardiac contraction and relaxation in failing hearts. The therapeutic potential of cBIN1 gene therapy is enormous given its ability to rescue cardiac inotropy and provide lusitropic protection in the meantime. These unprecedented capabilities of cBIN1 gene therapy are shifting the current paradigm of therapy development for heart failure, particularly HFpEF.
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