Vascular rho kinases and their potential therapeutic applications

Current Opinion in Drug Discovery and Development

Volumn 10, Issue 5, 2007, Pages 590-596

  Budzyn, K ^a   Sobey, C G ^b  

^a UNIVERSITY OF MELBOURNE   (Australia)

^b MONASH UNIVERSITY   (Australia)

Author keywords

Endothelium; Nitric oxide; Rho kinase; Statins; Vascular smooth muscle

Indexed keywords

4 (1 AMINOETHYL) N (4 PYRIDYL)CYCLOHEXANECARBOXAMIDE; ANGIOTENSIN II; CALCIUM; ENDOTHELIN 1; FASUDIL; G PROTEIN COUPLED RECEPTOR; GSK 269962A; H 1152; HYDROXYFASUDIL; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; INDAZOLE DERIVATIVE; MYOSIN LIGHT CHAIN KINASE; PROTEIN KINASE C; PYRIDONE DERIVATIVE; RHO KINASE; RHO KINASE INHIBITOR; SB 772077B; TRANSFERASE INHIBITOR; UNCLASSIFIED DRUG;

BLOOD VESSEL FUNCTION; BLOOD VESSEL TONE; BRAIN ISCHEMIA; BRAIN VASOSPASM; DRUG EFFECT; DRUG MECHANISM; DRUG SAFETY; ENZYME INHIBITION; ENZYME PHOSPHORYLATION; ENZYME REGULATION; HUMAN; HYPERTENSION; NONHUMAN; PROTEIN EXPRESSION; PROTEIN TARGETING; REVIEW; SMOOTH MUSCLE CONTRACTION; VASCULAR SMOOTH MUSCLE; VASOCONSTRICTION;

ANIMALS; CARDIOVASCULAR DISEASES; DRUG DESIGN; ENDOTHELIUM, VASCULAR; ENZYME INHIBITORS; HUMANS; MOLECULAR STRUCTURE; MUSCLE, SMOOTH, VASCULAR; RHO-ASSOCIATED KINASES;

EID: 34548381768     PISSN: 13676733     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (48)

1. Etienne-Manneville S, Hall A: Rho GTPases in cell biology. Nature (2002) 420(6916):629-635.
2. 2C-adrenoceptor translocation. Circ Res (2004) 94(10):1367-1374.
3. Dubroca C, You D, Levy BI, Loufrani L, Henrion D: Involvement of rhoA/rho kinase pathway in myogenic tone in the rabbit facial vein. Hypertension (2005) 45(5):974-979.
4. Lan C, Das D, Wloskowicz A, Vollrath B: Endothelin-1 modulates hemoglobin-mediated signaling in cerebrovascular smooth muscle via rhoA/rho kinase and protein kinase C. Am J Physiol Heart Circ Physiol (2004) 286(1):H165-H173.
5. Leung T, Chen XQ, Manser E, Lim L: The p160 rhoA-binding kinase ROKα is a member of a kinase family and is involved in the reorganization of the cytoskeleton. Mol Cell Biol (1996) 16(10):5313-5327.
6. Riento K, Ridley AJ: ROCKS: Multifunctional kinases in cell behaviour. Nat Rev Mol Cell Biol (2003) 4(6):446-456. •• Provides a comprehensive review of rho kinase structure, regulation and roles in cell biology.
7. Budzyn K, Marley PD, Sobey CG: Targeting rho and rho-kinase in the treatment of cardiovascular disease. Trends Pharmacol Sci (2006) 27(2):97-104. • Provides a comprehensive review of the most recent evidence for rho and rho kinase involvement in the development of several cardiovascular disorders.
8. Somlyo AP, Somlyo AV: Signal transduction by G-proteins, rho-kinase and protein phosphatase to smooth muscle and non-muscle myosin II. J Physiol (2000) 522(Pt 2):177-185.
9. 2+ sensitivity of smooth muscle and nonmuscle myosin II: Modulated by G proteins, kinases, and myosin phosphatase. Physiol Rev (2003) 83(4):1325-1358.
10. 2+-sensitization-induced contraction of smooth muscle.
11. Amano M, Chihara K, Nakamura N, Kaneko T, Matsuura Y, Kaibuchi K: The COOH terminus of rho-kinase negatively regulates rho-kinase activity. J Biol Chem (1999) 274(45):32418-32424.
12. Chen XQ, Tan I, Ng CH, Hall C, Lim L, Leung T: Characterisation of rhoA-binding kinase ROKα implication of the pleckstrin homology domain in ROKα function using region-specific antibodies. J Biol Chem (2002) 277(15):12680-12688.
13. Amano M, Chihara K, Kimura K, Fukata Y, Nakamura N, Matsuura Y, Kaibuchi K: Formation of actin stress fibers and focal adhesions enhanced by rho-kinase. Science (1997) 275(5304):1308-1311.
14. Uehata M, Ishizaki T, Satoh H, Ono T, Kawahara T, Morishita T, Tamakawa H, Yamagami K, Inui J, Maekawa M, Narumiya S: Calcium sensitization of smooth muscle mediated by a rho-associated protein kinase in hypertension. Nature (1997) 389(6654):990-994. •• Describes the first demonstration that rho kinase might be associated with the development of hypertension.
15. Chrissobolis S, Sobey CG: Evidence that rho-kinase activity contributes to cerebral vascular tone in vivo and is enhanced during chronic hypertension: Comparison with protein kinase C. Circ Res (2001) 88(8):774-779. •• Describes the first direct demonstration that rho kinase is an important regulator of vascular tone in vivo, particularly under conditions of chronic hypertension.
16. Jin L, Ying Z, Hilgers RH, Yin J, Zhao X, Imig JD, Webb RC: Increased rhoA/rho-kinase signaling mediates spontaneous tone in aorta from angiotensin II-induced hypertensive rats. J Pharmacol Exp Ther (2006) 318(1):288-295.
17. Ito K, Hirooka Y, Kishi T, Kimura Y, Kaibuchi K, Shimokawa H, Takeshita A: Rho/rho-kinase pathway in the brainstem contributes to hypertension caused by chronic nitric oxide synthase inhibition. Hypertension (2004) 43(2):156-162.
18. Moriki N, Ito M, Seko T, Kureishi Y, Okamoto R, Nakakuki T, Kongo M, Isaka N, Kaibuchi K, Nakano T: RhoA activation in vascular smooth muscle cells from stroke-prone spontaneously hypertensive rats. Hypertens Res (2004) 27(4):263-270.
19. Shin HK, Salomone S, Potts EM, Lee SW, Millican E, Noma K, Huang PL, Boas DA, Liao JK, Moskowitz MA, Ayata C: Rho-kinase inhibition acutely augments blood flow in focal cerebral ischemia via endothelial mechanisms. J Cereb Blood Flow Metab (2007) 27(5):998-1009.
20. Mita S, Kobayashi N, Yoshida K, Nakano S, Matsuoka H: Cardioprotective mechanisms of rho-kinase inhibition associated with eNOS and oxidative stress-LOX-1 pathway in Dahl salt-sensitive hypertensive rats. J Hypertens (2005) 23(1):87-96.
21. Davies SP, Reddy H, Caivano M, Cohen P: Specificity and mechanism of action of some commonly used protein kinase inhibitors. Biochem J (2000) 351(Pt 1):95-105. •• Describes an important study directly testing the inhibitory properties of several widely used protein kinase inhibitors, including Y-27632 and fasudil.
22. Budzyn K, Paull M, Marley PD, Sobey CG: Segmental differences in the roles of rho-kinase and protein kinase C in mediating vasoconstriction. J Pharmacol Exp Ther (2006) 317(2):791-796.
23. Kandabashi T, Shimokawa H, Miyata K, Kunihiro I, Eto Y, Morishige K, Matsumoto Y, Obara K, Nakayama K, Takahashi S, Takeshita A: Evidence for protein kinase C-mediated activation of rho-kinase in a porcine model of coronary artery spasm. Arterioscler Thromb Vasc Biol (2003) 23(12): 2209-2214.
24. Noma K, Goto C, Nishioka K, Jitsuiki D, Umemura T, Ueda K, Kimura M, Nakagawa K, Oshima T, Chayama K, Yoshizumi M et al: Roles of rho-associated kinase and oxidative stress in the pathogenesis of aortic stiffness. J Am Coll Cardiol (2007) 49(6):698-705.
25. Nohria A, Grunert ME, Rikitake Y, Noma K, Prsic A, Ganz P, Liao JK, Creager MA: Rho kinase inhibition improves endothelial function in human subjects with coronary artery disease. Circ Res (2006) 99(12):1426-1432.
26. Kishi T, Hirooka Y, Masumoto A, Ito K, Kimura Y, Inokuchi K, Tagawa T, Shimokawa H, Takeshita A, Sunagawa K: Rho-kinase inhibitor improves increased vascular resistance and impaired vasodilation of the forearm in patients with heart failure. Circulation (2005) 111(21):2741-2747.
27. Jacobs M, Hayakawa K, Swenson L, Bellon S, Fleming M, Taslimi P, Doran J: The structure of dimeric ROCKI reveals the mechanism for ligand selectivity. J Biol Chem (2006) 281(1):260-268. •• Provides new insight into the basis of selectivity of four important inhibitors of rho kinase.
28. Ikenoya M, Hidaka H, Hosoya T, Suzuki M, Yamamoto N, Sasaki Y: Inhibition of rho-kinase-induced myristoylated alanine-rich C kinase substrate (MARCKS) phosphorylation in human neuronal cells by H-1152, a novel and specific rho-kinase inhibitor. J Neurochem (2002) 81(1):9-16.
29. Teixeira CE, Ying Z, Webb RC: Proerectile effects of the rho-kinase inhibitor (S)-(+)-2-methyl-1-[(4-methyl-5-isoquinolinyl)sulfonyl]homopiperazine (H-1152) in the rat penis. J Pharmacol Exp Ther (2005) 315(1):155-162.
30. Goodman KB, Cui H, Dowdell SE, Gaitanopoulos DE, Ivy RL, Sehon CA, Stavenger RA, Wang GZ, Viet AQ, Xu W, Ye G et al: Development of dihydropyridone indazole amides as selective rho-kinase inhibitors. J Med Chem (2007) 50(1):6-9.
31. Doe C, Bentley R, Behm DJ, Lafferty R, Stavenger R, Jung D, Bamford M, Panchal T, Grygielko E, Wright LL, Smith GK et al: Novel rho kinase inhibitors with anti-inflammatory and vasodilatory activities. J Pharmacol Exp Ther (2007) 320(1):89-98.
32. Salamanca DA, Khalil RA: Protein kinase C isoforms as specific targets for modulation of vascular smooth muscle function in hypertension. Biochem Pharmacol (2005) 70(11):1537-1547.
33. Faraci FM, Lamping KG, Modrick ML, Ryan MJ, Sigmund CD, Didion SP: Cerebral vascular effects of angiotensin II: New insights from genetic models. J Cereb Blood Flow Metab (2006) 26(4):449-455.
34. 1A receptor in mice. Hypertension (2004) 43(5):1074-1079.
35. Wehrwein EA, Northcott CA, Loberg RD, Watts SW: Rho/rho kinase and phosphoinositide 3-kinase are parallel pathways in the development of spontaneous arterial tone in deoxycorticosterone acetate-salt hypertension. J Pharmacol Exp Ther (2004) 309(3):1011-1019. • Provides evidence that rho kinase, as well as vascular smooth muscle PI3K, might each have roles in the development of hypertension in a deoxycorticosterone acetate salt animal model.
36. Rikitake Y, Liao JK: Rho-kinase mediates hyperglycemia-induced plasminogen activator inhibitor-1 expression in vascular endothelial cells. Circulation (2005) 111(24):3261-3268.
37. Liao JK, Laufs U: Pleiotropic effects of statins. Annu Rev Pharmacol Toxicol (2005) 45:89-118. • Provides a comprehensive review of the vascular effects of statins.
38. Goldstein JL, Brown MS: Regulation of the mevalonate pathway. Nature (1990) 343(6257):425-430.
39. Laufs U, Liao JK: Post-transcriptional regulation of endothelial nitric oxide synthase mRNA stability by rho GTPase. J Biol Chem (1998) 273(37):24266-24271. •Provides the first evidence of negative regulation of eNOS messenger RNA by rhoA, and that this inhibition can be relieved by statin treatment.
40. Laufs U, La Fata V, Plutzky J, Liao JK: Upregulation of endothelial nitric oxide synthase by HMG-CoA reductase inhibitors. Circulation (1998) 97(12):1129-1135.
41. Shiga N, Hirano K, Hirano M, Nishimura J, Nawata H, Kanaide H: Long-term inhibition of rhoA attenuates vascular contractility by enhancing endothelial NO production in an intact rabbit mesenteric artery. Circ Res (2005) 96(9):1014-1021. •• Describes the first functional evidence of statin-induced increases in NO production leading to alterations in vascular contractility.
42. Budzyn K, Marley PD, Sobey CG: Chronic mevastatin modulates receptor-dependent vascular contraction in eNOS-deficient mice. Am J Physiol Regul Integr Comp Physiol (2004) 287(2):R342-R348.
43. Girgis RE, Mozammel S, Champion HC, Li D, Peng X, Shimoda LA, Tuder RM, Johns RA, Hassoun PM: Regression of chronic hypoxic pulmonary hypertension by simvastatin. Am J Physiol Lung Cell Mol Physiol (2007) 292(5):L1105-L1110.
44. Yamanouchi D, Banno H, Nakayama M, Sugimoto M, Fujita H, Kobayashi M, Kuwano H, Komori K: Hydrophilic statin suppresses vein graft intimal hyperplasia via endothelial cell-tropic rho-kinase inhibition. J Vasc Surg (2005) 42(4):757-764.
45. Wolfrum S, Dendorfer A, Rikitake Y, Stalker TJ, Gong Y, Scalia R, Dominiak P, Liao JK: Inhibition of rho-kinase leads to rapid activation of phosphatidylinositol 3-kinase/protein kinase Akt and cardiovascular protection. Arterioscler Thromb Vasc Biol (2004) 24(10):1842- 1847. • Provides evidence for negative regulation of PI3K by rho kinase within the endothelium.
46. Budzyn K, Marley PD, Sobey CG: Opposing roles of endothelial and smooth muscle phosphatidylinositol 3-kinase in vasoconstriction: Effects of rho-kinase and hypertension. J Pharmacol Exp Ther (2005) 313(3):1248-1253.
47. Ming XF, Barandier C, Viswambharan H, Kwak BR, Mach F, Mazzolai L, Hayoz D, Ruffieux J, Rusconi S, Montani JP, Yang Z: Thrombin stimulates human endothelial arginase enzymatic activity via rhoA/ROCK pathway: Implications for atherosclerotic endothelial dysfunction. Circulation (2004) 110(24):3708-3714. •• Provides the first evidence that rhoA/rho kinase might induce endothelial dysfunction via arginase.
48. Rikitake Y, Kim HH, Huang Z, Seto M, Yano K, Asano T, Moskowitz MA, Liao JK: Inhibition of rho kinase (ROCK) leads to increased cerebral blood flow and stroke protection. Stroke (2005) 36(10):2251-2257.