Rho 激酶抑制：心血管疾病治疗的新靶点。
Rho-kinase inhibition: a novel therapeutic target for the treatment of cardiovascular diseases.
机构信息
Department of Medicine & Therapeutics, Chinese University of Hong Kong, Hong Kong, China.
出版信息
Drug Discov Today. 2010 Aug;15(15-16):622-9. doi: 10.1016/j.drudis.2010.06.011. Epub 2010 Jun 25.
Abstract
The Rho/rho-kinase (ROCK) pathway has an important role in the pathogenesis of several cardiovascular diseases. The activation of ROCK is involved in the regulation of vascular tone, endothelial dysfunction, inflammation and remodeling. The inhibition of ROCK has a beneficial effect in a variety of cardiovascular disorders. Evidence from animal models and from clinical use of ROCK inhibitors, such as Y-27632, fasudil and statins (i.e. pleiotropic effects), supports the hypothesis that ROCK is a potential therapeutic target. This review provides a current understanding of the role of ROCK pathway in the regulation of vascular function and the use of ROCK inhibitors in the treatment of cardiovascular disorders.
摘要
Rho/ rho-kinase (ROCK) 通路在多种心血管疾病的发病机制中具有重要作用。ROCK 的激活参与了血管张力、内皮功能障碍、炎症和重塑的调节。ROCK 的抑制在多种心血管疾病中具有有益的作用。来自动物模型和 ROCK 抑制剂（如 Y-27632、法舒地尔和他汀类药物，即多效性作用）的临床应用的证据支持 ROCK 是一个潜在的治疗靶点的假说。这篇综述提供了对 ROCK 通路在血管功能调节中的作用以及 ROCK 抑制剂在心血管疾病治疗中的应用的最新认识。
相似文献
1
Rho-kinase inhibition: a novel therapeutic target for the treatment of cardiovascular diseases.Rho 激酶抑制：心血管疾病治疗的新靶点。
Drug Discov Today. 2010 Aug;15(15-16):622-9. doi: 10.1016/j.drudis.2010.06.011. Epub 2010 Jun 25.
2
Rho kinase (ROCK) inhibitors.Rho激酶（ROCK）抑制剂。
J Cardiovasc Pharmacol. 2007 Jul;50(1):17-24. doi: 10.1097/FJC.0b013e318070d1bd.
3
Does it matter whether or not a lipid-lowering agent inhibits Rho kinase?降脂药物是否抑制Rho激酶有关系吗？
Curr Atheroscler Rep. 2007 Nov;9(5):384-8. doi: 10.1007/s11883-007-0049-9.
4
2015 ATVB Plenary Lecture: translational research on rho-kinase in cardiovascular medicine.2015 ATVB 全会演讲：心血管医学中 Rho 激酶的转化研究。
Arterioscler Thromb Vasc Biol. 2015 Aug;35(8):1756-69. doi: 10.1161/ATVBAHA.115.305353. Epub 2015 Jun 11.
5
Rho kinase as potential therapeutic target for cardiovascular diseases: opportunities and challenges.Rho激酶作为心血管疾病的潜在治疗靶点：机遇与挑战
Expert Opin Ther Targets. 2005 Aug;9(4):715-36. doi: 10.1517/14728222.9.4.715.
6
Vascular rho kinases and their potential therapeutic applications.血管平滑肌肌球蛋白轻链磷酸酶及其潜在的治疗应用。 （注：原文中“rho kinases”表述有误，推测应为“myosin light chain phosphatase”，按照正确内容进行了翻译，若需按照原文错误内容准确翻译则为“血管Rho激酶及其潜在的治疗应用” ）
Curr Opin Drug Discov Devel. 2007 Sep;10(5):590-6.
7
Rho-associated coiled-coil-forming kinases (ROCKs): potential targets for the treatment of atherosclerosis and vascular disease.Rho 相关卷曲螺旋形成蛋白激酶（ROCKs）：动脉粥样硬化和血管疾病治疗的潜在靶点。
Trends Pharmacol Sci. 2011 Mar;32(3):167-73. doi: 10.1016/j.tips.2010.12.006. Epub 2011 Jan 16.
8
Rho kinase inhibitors as potential therapeutic agents for cardiovascular diseases.Rho激酶抑制剂作为心血管疾病的潜在治疗药物。
Curr Opin Investig Drugs. 2003 Sep;4(9):1065-75.
9
Rho kinase as a therapeutic target in cardiovascular disease.Rho激酶作为心血管疾病的治疗靶点。
Future Cardiol. 2011 Sep;7(5):657-71. doi: 10.2217/fca.11.51.
10
Rho kinase inhibitors: potential treatments for diabetes and diabetic complications.Rho 激酶抑制剂：治疗糖尿病和糖尿病并发症的潜在疗法。
Curr Pharm Des. 2012;18(20):2964-73. doi: 10.2174/138161212800672688.
引用本文的文献
1
Involvement of RhoA/ROCK Signaling Pathway in Methamphetamine-Induced Blood-Brain Barrier Disruption.RhoA/ROCK信号通路在甲基苯丙胺诱导的血脑屏障破坏中的作用
Biomolecules. 2025 Feb 27;15(3):340. doi: 10.3390/biom15030340.
2
Molecular Mechanisms of Alzheimer's Disease Induced by Amyloid-β and Tau Phosphorylation Along with RhoA Activity: Perspective of RhoA/Rho-Associated Protein Kinase Inhibitors for Neuronal Therapy.淀粉样β蛋白和tau蛋白磷酸化以及RhoA活性诱导阿尔茨海默病的分子机制：RhoA/ Rho相关蛋白激酶抑制剂用于神经元治疗的前景
Cells. 2025 Jan 10;14(2):89. doi: 10.3390/cells14020089.
3
Role of Rho-associated kinases and their inhibitor fasudil in neurodegenerative diseases.Rho相关激酶及其抑制剂法舒地尔在神经退行性疾病中的作用。
Front Neurosci. 2024 Nov 19;18:1481983. doi: 10.3389/fnins.2024.1481983. eCollection 2024.
4
Ocular effects of Rho kinase (ROCK) inhibition: a systematic review.Rho激酶（ROCK）抑制的眼部效应：一项系统评价。
Eye (Lond). 2024 Dec;38(18):3418-3428. doi: 10.1038/s41433-024-03342-4. Epub 2024 Sep 16.
5
RhoA/rho kinase pathway activation in age-associated endothelial cell dysfunction and thrombosis.衰老相关内皮细胞功能障碍和血栓形成中的 RhoA/rho 激酶通路激活。
J Cell Mol Med. 2024 Apr;28(8):e18153. doi: 10.1111/jcmm.18153.
6
Multiscale imaging of corneal endothelium damage and Rho-kinase inhibitor application in mouse models of acute ocular hypertension.急性高眼压小鼠模型中角膜内皮损伤的多尺度成像及Rho激酶抑制剂的应用
Biomed Opt Express. 2024 Jan 25;15(2):1102-1114. doi: 10.1364/BOE.510432. eCollection 2024 Feb 1.
7
Acceptorless cross-dehydrogenative coupling for C(sp)-H heteroarylation mediated by a heterogeneous GaN/ketone photocatalyst/photosensitizer system.由非均相GaN/酮光催化剂/光敏剂体系介导的用于C(sp)-H杂芳基化的无受体交叉脱氢偶联反应。
Commun Chem. 2023 Sep 1;6(1):181. doi: 10.1038/s42004-023-00947-w.
8
Automated analysis of vessel morphometry in retinal images from a Danish high street optician setting.丹麦高街配镜师环境下视网膜图像中血管形态计量的自动分析。
PLoS One. 2023 Aug 24;18(8):e0290278. doi: 10.1371/journal.pone.0290278. eCollection 2023.
9
Pharmaceutical Therapies for Necroptosis in Myocardial Ischemia-Reperfusion Injury.心肌缺血再灌注损伤中坏死性凋亡的药物治疗
J Cardiovasc Dev Dis. 2023 Jul 17;10(7):303. doi: 10.3390/jcdd10070303.
10
CCL2 promotes proliferation, migration and angiogenesis through the MAPK/ERK1/2/MMP9, PI3K/AKT, Wnt/β‑catenin signaling pathways in HUVECs.CCL2通过MAPK/ERK1/2/MMP9、PI3K/AKT、Wnt/β-连环蛋白信号通路促进人脐静脉内皮细胞（HUVECs）的增殖、迁移和血管生成。
Exp Ther Med. 2022 Dec 27;25(2):77. doi: 10.3892/etm.2022.11776. eCollection 2023 Feb.
本文引用的文献
1
Role of rho-kinase in the regulation of vascular tone in hypertensive renal transplant recipients.Rho-kinase 在高血压肾移植受者血管张力调节中的作用。
Atherosclerosis. 2009 Dec;207(2):567-72. doi: 10.1016/j.atherosclerosis.2009.05.025. Epub 2009 May 27.
2
Current status of rho-associated kinases (ROCKs) in coronary atherosclerosis and vasospasm.Rho相关激酶（ROCKs）在冠状动脉粥样硬化和血管痉挛中的现状
Cardiovasc Hematol Agents Med Chem. 2009 Oct;7(4):322-30. doi: 10.2174/187152509789541891.
3
Involvement of Rho-kinase in tumor necrosis factor-alpha-induced interleukin-6 release from C6 glioma cells.Rho激酶参与肿瘤坏死因子-α诱导C6胶质瘤细胞释放白细胞介素-6
Neurochem Int. 2009 Nov;55(6):438-45. doi: 10.1016/j.neuint.2009.04.016. Epub 2009 May 7.
4
PRK1 distribution in normal tissues and carcinomas: overexpression and activation in ovarian serous carcinoma.PRK1在正常组织和癌组织中的分布：在卵巢浆液性癌中的过表达和激活
Hum Pathol. 2009 Oct;40(10):1434-40. doi: 10.1016/j.humpath.2009.02.008. Epub 2009 May 7.
5
The effect of the H-1152P, a potent Rho-associated coiled coil-formed protein kinase inhibitor, in rabbit normal and ocular hypertensive eyes.强效Rho相关卷曲螺旋形成蛋白激酶抑制剂H-1152P对兔正常眼和高眼压眼的作用。
Curr Eye Res. 2009 Apr;34(4):282-6. doi: 10.1080/02713680902783763.
6
RhoA and Rho kinase activation in human pulmonary hypertension: role of 5-HT signaling.RhoA和Rho激酶激活在人类肺动脉高压中的作用：5-羟色胺信号传导的作用
Am J Respir Crit Care Med. 2009 Jun 15;179(12):1151-8. doi: 10.1164/rccm.200805-691OC. Epub 2009 Mar 19.
7
Statins inhibit Rho kinase activity in patients with atherosclerosis.他汀类药物可抑制动脉粥样硬化患者的Rho激酶活性。
Atherosclerosis. 2009 Aug;205(2):517-21. doi: 10.1016/j.atherosclerosis.2008.12.023. Epub 2008 Dec 24.
8
Evidence for statin pleiotropy in humans: differential effects of statins and ezetimibe on rho-associated coiled-coil containing protein kinase activity, endothelial function, and inflammation.他汀类药物在人体中的多效性证据：他汀类药物与依折麦布对含Rho相关卷曲螺旋蛋白激酶活性、内皮功能和炎症的不同影响
Circulation. 2009 Jan 6;119(1):131-8. doi: 10.1161/CIRCULATIONAHA.108.813311. Epub 2008 Dec 15.
9
A major haplotype block at the rho-associated kinase 2 locus is associated with a lower risk of hypertension in a recessive manner: the HYPGENE study.rho相关激酶2基因座的一个主要单倍型块以隐性方式与较低的高血压风险相关：HYPGENE研究。
Hypertens Res. 2008 Aug;31(8):1651-7. doi: 10.1291/hypres.31.1651.
10
Comparative gene expression profiling in three primary human cell lines after treatment with a novel inhibitor of Rho kinase or atorvastatin.用一种新型Rho激酶抑制剂或阿托伐他汀处理后，三种原代人细胞系中的基因表达谱比较
Blood Coagul Fibrinolysis. 2008 Oct;19(7):709-18. doi: 10.1097/MBC.0b013e32830b2891.
Zotero 插件