Targeting Rho-associated coiled-coil forming protein kinase (ROCK) in cardiovascular fibrosis and stiffening.
Targeting Rho-associated coiled-coil forming protein kinase (ROCK) in cardiovascular fibrosis and stiffening.
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靶向Rho相关卷曲螺旋形成蛋白激酶（ROCK）在心血管纤维化和硬化中的作用
DOI：
10.1080/14728222.2020.1712593
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发表时间：
2020-01
影响因子：
5.8
通讯作者：
Liao JK
中科院分区：
文献类型：
--
作者：
Yu B;Sladojevic N;Blair JE;Liao JK
病理性心脏纤维化，通过纤维母细胞细胞外基质蛋白沉积过多、促纤维化免疫反应和血管硬化，与大多数形式的心血管疾病有关。病理性心脏纤维化和硬化可导致心力衰竭和心律失常，血管硬化可导致高血压。ROCK是gtpase rho家族下游的一种丝氨酸/苏氨酸激酶，可能在许多细胞类型中调节许多促纤维化和促硬化信号通路。本文概述了ROCK在成纤维细胞、T辅助细胞、内皮细胞、血管平滑肌细胞和巨噬细胞中介导纤维化和硬化的分子机制。我们推测ROCK如何能够靶向抑制心血管纤维化和硬化。如果ROCK抑制剂要用于临床，就必须解决知识上的关键空白。大量研究表明，每种ROCK异构体在调节纤维化中可能发挥不同的作用，在特定组织中可能具有相反的作用。未来的工作需要强调ROCK在纤维化中的异构体和组织特异性贡献，以及小鼠模型和临床试验中异构体特异性ROCK抑制剂如何影响心脏纤维化和硬化的病理生理。这可能会促进对心力衰竭、心律失常和高血压的新治疗方法以及心肌梗死后修复过程的认识。
Pathological cardiac fibrosis, through excessive extracellular matrix protein deposition from fibroblasts and pro-fibrotic immune responses and vascular stiffening is associated with most forms of cardiovascular disease. Pathological cardiac fibrosis and stiffening can lead to heart failure and arrythmias and vascular stiffening may lead to hypertension. ROCK, a serine/threonine kinase downstream of the Rho-family of GTPases, may regulate many pro-fibrotic and pro-stiffening signaling pathways in numerous cell types. This article outlines the molecular mechanisms by which ROCK in fibroblasts, T helper cells, endothelial cells, vascular smooth muscle cells, and macrophages mediate fibrosis and stiffening. We speculate on how ROCK could be targeted to inhibit cardiovascular fibrosis and stiffening. Critical gaps in knowledge must be addressed if ROCK inhibitors are to be used in the clinic. Numerous studies indicate that each ROCK isoform may play differential roles in regulating fibrosis and may have opposing roles in specific tissues. Future work needs to highlight the isoform- and tissue-specific contributions of ROCK in fibrosis, and how isoform-specific ROCK inhibitors in murine models and in clinical trials affect the pathophysiology of cardiac fibrosis and stiffening. This could progress knowledge regarding new treatments for heart failure, arrythmias and hypertension and the repair processes after myocardial infarction.
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影响因子：
20.1
作者：
Eto, M;Barandiér, C;Lüscher, TF
通讯作者：
Lüscher, TF
影响因子：
3.2
作者：
Gabrielli, Luigi;Winter, Jose L.;Jalil, Jorge E.
通讯作者：
Jalil, Jorge E.
DOI：
10.1513/pats.200705-057vs
发表时间：
2008-01-01
期刊：
Proceedings of the American Thoracic Society
影响因子：
--
作者：
Halayko, Andrew J;Tran, Thai;Gosens, Reinoud
通讯作者：
Gosens, Reinoud
影响因子：
7.3
作者：
Feng, Yangbo;LoGrasso, Philip V.;Li, Rongshi
通讯作者：
Li, Rongshi
影响因子：
18.2
作者：
Dong, Ming;Liao, James K.;Yu, Cheuk-Man
通讯作者：
Yu, Cheuk-Man