Rho Kinase Signaling and Cardiac Physiology

Overview

Journal Curr Opin Physiol

Date 2018 Mar 13

PMID 29527586

Citations 14

Authors

Yuan Dai

Weijia Luo

Jiang Chang

Affiliations

Soon will be listed here.

Abstract

Rho kinases (ROCKs) are the first discovered RhoA effectors that are now widely known for their effects on actin organization. Recent studies have shown that ROCKs play important roles in cardiac physiology. Abnormal activation of ROCKs participate in multiple cardiovascular pathological processes, including cardiac hypertrophy, apoptosis, fibrosis, systemic hypertension, and pulmonary hypertension. ROCK inhibitors, fasudil and statins, have shown beneficial cardiovascular effects in many animal studies, clinical trials, and applications. Here, we mainly discuss the current understanding of the physiological roles of Rho kinase signaling in the heart, and briefly summarize the roles of ROCKs in cardiac-related vascular dysfunctions. We will also discuss the clinical application of ROCK inhibitors.

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References

Yang X, Wang T, Lin X, Yue X, Wang Q, Wang G . Genetic deletion of Rnd3/RhoE results in mouse heart calcium leakage through upregulation of protein kinase A signaling. Circ Res. 2014; 116(1):e1-e10. PMC: 4282622. DOI: 10.1161/CIRCRESAHA.116.304940. View

Corrado D, Link M, Calkins H . Arrhythmogenic Right Ventricular Cardiomyopathy. N Engl J Med. 2017; 376(1):61-72. DOI: 10.1056/NEJMra1509267. View

Jie W, Andrade K, Lin X, Yang X, Yue X, Chang J . Pathophysiological Functions of Rnd3/RhoE. Compr Physiol. 2016; 6(1):169-86. PMC: 4842315. DOI: 10.1002/cphy.c150018. View

Gabrielli L, Winter J, Godoy I, McNab P, Padilla I, Cordova S . Increased rho-kinase activity in hypertensive patients with left ventricular hypertrophy. Am J Hypertens. 2013; 27(6):838-45. DOI: 10.1093/ajh/hpt234. View

Riento K, Guasch R, Garg R, Jin B, Ridley A . RhoE binds to ROCK I and inhibits downstream signaling. Mol Cell Biol. 2003; 23(12):4219-29. PMC: 156133. DOI: 10.1128/MCB.23.12.4219-4229.2003. View

Pinner S, Sahai E . PDK1 regulates cancer cell motility by antagonising inhibition of ROCK1 by RhoE. Nat Cell Biol. 2008; 10(2):127-37. DOI: 10.1038/ncb1675. View

Nakagawa O, Fujisawa K, Ishizaki T, Saito Y, Nakao K, Narumiya S . ROCK-I and ROCK-II, two isoforms of Rho-associated coiled-coil forming protein serine/threonine kinase in mice. FEBS Lett. 1996; 392(2):189-93. DOI: 10.1016/0014-5793(96)00811-3. View

Shibuya M, Hirai S, Seto M, Satoh S, Ohtomo E . Effects of fasudil in acute ischemic stroke: results of a prospective placebo-controlled double-blind trial. J Neurol Sci. 2005; 238(1-2):31-9. DOI: 10.1016/j.jns.2005.06.003. View

Yang X, Li Q, Lin X, Ma Y, Yue X, Tao Z . Mechanism of fibrotic cardiomyopathy in mice expressing truncated Rho-associated coiled-coil protein kinase 1. FASEB J. 2012; 26(5):2105-16. PMC: 3336781. DOI: 10.1096/fj.11-201319. View

10.

Zhang Y, Bo J, Taffet G, Chang J, Shi J, Reddy A . Targeted deletion of ROCK1 protects the heart against pressure overload by inhibiting reactive fibrosis. FASEB J. 2006; 20(7):916-25. DOI: 10.1096/fj.05-5129com. View

11.

Mera C, Godoy I, Ramirez R, Moya J, Ocaranza M, Jalil J . Mechanisms of favorable effects of Rho kinase inhibition on myocardial remodeling and systolic function after experimental myocardial infarction in the rat. Ther Adv Cardiovasc Dis. 2015; 10(1):4-20. PMC: 5933601. DOI: 10.1177/1753944715609516. View

12.

Dvorsky R, Blumenstein L, Vetter I, Ahmadian M . Structural insights into the interaction of ROCKI with the switch regions of RhoA. J Biol Chem. 2003; 279(8):7098-104. DOI: 10.1074/jbc.M311911200. View

13.

Patel P, Parikh M, Shah H, Gandhi T . Inhibition of RhoA/Rho kinase by ibuprofen exerts cardioprotective effect on isoproterenol induced myocardial infarction in rats. Eur J Pharmacol. 2016; 791:91-98. DOI: 10.1016/j.ejphar.2016.08.015. View

14.

Sacks F, Pfeffer M, Moye L, Rouleau J, Rutherford J, Cole T . The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. Cholesterol and Recurrent Events Trial investigators. N Engl J Med. 1996; 335(14):1001-9. DOI: 10.1056/NEJM199610033351401. View

15.

Amano M, Chihara K, Kimura K, Fukata Y, Nakamura N, Matsuura Y . Formation of actin stress fibers and focal adhesions enhanced by Rho-kinase. Science. 1997; 275(5304):1308-11. DOI: 10.1126/science.275.5304.1308. View

16.

Schofield A, Bernard O . Rho-associated coiled-coil kinase (ROCK) signaling and disease. Crit Rev Biochem Mol Biol. 2013; 48(4):301-16. DOI: 10.3109/10409238.2013.786671. View

17.

Fukumoto Y, Mohri M, Inokuchi K, Ito A, Hirakawa Y, Masumoto A . Anti-ischemic effects of fasudil, a specific Rho-kinase inhibitor, in patients with stable effort angina. J Cardiovasc Pharmacol. 2007; 49(3):117-21. DOI: 10.1097/FJC.0b013e31802ef532. View

18.

Bid H, Roberts R, Manchanda P, Houghton P . RAC1: an emerging therapeutic option for targeting cancer angiogenesis and metastasis. Mol Cancer Ther. 2013; 12(10):1925-34. PMC: 3823055. DOI: 10.1158/1535-7163.MCT-13-0164. View

19.

Shibuya M, Suzuki Y . [Treatment of cerebral vasospasm by a protein kinase inhibitor AT 877]. No To Shinkei. 1993; 45(9):819-24. View

20.

Coleman M, Sahai E, Yeo M, Bosch M, Dewar A, Olson M . Membrane blebbing during apoptosis results from caspase-mediated activation of ROCK I. Nat Cell Biol. 2001; 3(4):339-45. DOI: 10.1038/35070009. View