Rho GTPases in pulmonary vascular dysfunction

Vascular Pharmacology

Volumn 58, Issue 3, 2013, Pages 202-210

  Storck, Elisabeth M ^a   Wojciak Stothard, Beata ^a  

^a IMPERIAL COLLEGE LONDON   (United Kingdom)

Author keywords

Disease; Pulmonary; Rho GTPases; Therapy; Vascular

Indexed keywords

4 (1 AMINOETHYL) N (4 PYRIDYL)CYCLOHEXANECARBOXAMIDE; ANTICOAGULANT AGENT; ANTIINFLAMMATORY AGENT; BONE MORPHOGENETIC PROTEIN; CIGARETTE SMOKE; CYTOKINE; ENDOTHELIN RECEPTOR ANTAGONIST; FASUDIL; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; IMATINIB; MICRORNA; PHOSPHODIESTERASE V INHIBITOR; PROSTACYCLIN; PROSTANOID; PROTEIN CDC42; RAC1 PROTEIN; RHO GUANINE NUCLEOTIDE BINDING PROTEIN; RHO KINASE; RHOA GUANINE NUCLEOTIDE BINDING PROTEIN; RHOB GUANINE NUCLEOTIDE BINDING PROTEIN; SILDENAFIL; SIMVASTATIN;

ACUTE LUNG INJURY; ADULT RESPIRATORY DISTRESS SYNDROME; ARTICLE; CELL ADHESION; CELL HYPOXIA; CELL MIGRATION; CELL PROLIFERATION; CELL SURVIVAL; CELL VACUOLE; CHRONIC OBSTRUCTIVE LUNG DISEASE; DRUG EFFICACY; DRUG TARGETING; ENVIRONMENTAL FACTOR; ENZYME ACTIVITY; GENE EXPRESSION; HUMAN; INFLAMMATION; INTRACELLULAR TRANSPORT; LUNG EMBOLISM; MECHANICAL STRESS; MEMBRANE MICROPARTICLE; METABOLIC STRESS; MORPHOGENESIS; NONHUMAN; OXIDATIVE STRESS; PRIORITY JOURNAL; PULMONARY HYPERTENSION; PULMONARY VASCULAR DISEASE; REGULATORY MECHANISM; SMOOTH MUSCLE FIBER; VASCULAR SMOOTH MUSCLE;

ACTINS; ANIMALS; HUMANS; HYPERTENSION, PULMONARY; LUNG DISEASES; PULMONARY CIRCULATION; RHO GTP-BINDING PROTEINS; VASCULAR DISEASES;

EID: 84875373173     PISSN: 15371891     EISSN: 18793649     Source Type: Journal    
DOI: 10.1016/j.vph.2012.09.004     Document Type: Article

References (134)

1. Aaronson P.I., Robertson T., Knock G.A., Becker S., Lewis T.H., Snetkov V., Ward J.P. Hypoxic pulmonary vasoconstriction: mechanisms and controversies. J. Physiol. 2006, 570:53-58.
2. Abdul-Salam V.B., Wharton J., Cupitt J., Berryman M., Edwards R.J., Wilkins M.R. Proteomic analysis of lung tissues from patients with pulmonary arterial hypertension. Circulation 2010, 122:2058-2067.
3. Adamson P., Marshall C.J., Hall A., Tilbrook P.A. Post-translational modifications of p21rho proteins. J. Biol. Chem. 1992, 267:20033-20038.
4. Adini I., Rabinovitz I., Sun J.F., Prendergast G.C., Benjamin L.E. RhoB controls Akt trafficking and stage-specific survival of endothelial cells during vascular development. Genes Dev. 2003, 17:2721-2732.
5. Aghajanian A., Wittchen E.S., Campbell S.L., Burridge K. Direct activation of RhoA by reactive oxygen species requires a redox-sensitive motif. PLoS One 2009, 4:e8045. 10.1371/journal.pone.0008045.
6. Amabile N., Heiss C., Real W.M., Minasi P., McGlothlin D., Rame E.J., Grossman W., De Marco T., Yeghiazarians Y. Circulating endothelial microparticle levels predict hemodynamic severity of pulmonary hypertension. Am. J. Respir. Crit. Care Med. 2008, 177:1268-1275.
7. Aoki H., Izumo S., Sadoshima J. Angiotensin II activates RhoA in cardiac myocytes - a critical role of RhoA in angiotensin II-induced premyofibril formation. Circ. Res. 1998, 82:666-676.
8. Archer S.L., Weir E.K., Wilkins M.R. Basic science of pulmonary arterial hypertension for clinicians: new concepts and experimental therapies. Circulation 2010, 121:2045-2066.
9. Arrigoni F.I., Vallance P., Haworth S.G., Leiper J.M. Metabolism of asymmetric dimethylarginines is regulated in the lung developmentally and with pulmonary hypertension induced by hypobaric hypoxia. Circulation 2003, 107:1195-1201.
10. Bakouboula B., Morel O., Faure A., Zobairi F., Jesel L., Trinh A., Zupan M., Canuet M., Grunebaum L., Brunette A., Desprez D., Chabot F., Weitzenblum E., Freyssinet J.M., Chaouat A., Toti F. Procoagulant membrane microparticles correlate with the severity of pulmonary arterial hypertension. Am. J. Respir. Crit. Care Med. 2008, 177:536-543.
11. Bear M.D., Li M., Liu Y., Giel-Moloney M.A., Fanburg B.L., Toksoz D. The Lbc Rho guanine nucleotide exchange factor alpha-catulin axis functions in serotonin-induced vascular smooth muscle cell mitogenesis and RhoA/ROCK activation. J. Biol. Chem. 2010, 285:32919-32926.
12. Beckers C.M., van Hinsbergh V.W., van Nieuw Amerongen G.P. Driving Rho GTPase activity in endothelial cells regulates barrier integrity. Thromb. Haemost. 2010, 103:40-55.
13. Birukova A.A., Smurova K., Birukov K.G., Kaibuchi K., Garcia J.G., Verin A.D. Role of Rho GTPases in thrombin-induced lung vascular endothelial cells barrier dysfunction. Microvasc. Res. 2004, 67:64-77.
14. Birukova A.A., Fu P., Xing J., Cokic I., Birukov K.G. Lung endothelial barrier protection by iloprost in the 2-hit models of ventilator-induced lung injury (VILI) involves inhibition of Rho signaling. Transl. Res. 2010, 155:44-54.
15. Birukova A.A., Tian Y., Meliton A., Leff A., Wu T., Birukov K.G. Stimulation of Rho signaling by pathologic mechanical stretch is a "second hit" to Rho-independent lung injury induced by IL-6. Am. J. Physiol. Lung Cell. Mol. Physiol. 2012, 302:L965-L975.
16. Bokoch G.M. Biology of the p21-activated kinases. Annu. Rev. Biochem. 2003, 72:743-781.
17. Boulanger C.M., Dignat-George F. Microparticles: an introduction. Arterioscler. Thromb. Vasc. Biol. 2011, 31:2-3.
18. 2+ sensitization in pulmonary vascular smooth muscle through superoxide-dependent stimulation of RhoA. Am. J. Physiol. Lung Cell. Mol. Physiol. 2010, 298:L232-L242.
19. Bryan B.A., D'Amore P.A. What tangled webs they weave: Rho-GTPase control of angiogenesis. Cell. Mol. Life Sci. 2007, 64:2053-2065.
20. Bryan B.A., Dennstedt E., Mitchell D.C., Walshe T.E., Noma K., Loureiro R., Saint-Geniez M., Campaigniac J.P., Liao J.K., D'Amore P.A. RhoA/ROCK signaling is essential for multiple aspects of VEGF-mediated angiogenesis. FASEB J. 2010, 24:3186-3195.
21. Budhiraja R., Tuder R.M., Hassoun P.M. Endothelial dysfunction in pulmonary hypertension. Circulation 2004, 109:159-165.
22. Burger D., Montezano A.C., Nishigaki N., He Y., Carter A., Touyz R.M. Endothelial microparticle formation by angiotensin II is mediated via Ang II receptor type I/NADPH oxidase/Rho kinase pathways targeted to lipid rafts. Arterioscler. Thromb. Vasc. Biol. 2011, 31:1898-1907.
23. Burton V.J., Ciuclan L.I., Holmes A.M., Rodman D.M., Walker C., Budd D.C. Bone morphogenetic protein receptor II regulates pulmonary artery endothelial cell barrier function. Blood 2011, 117:333-341.
24. Chi A.Y., Waypa G.B., Mungai P.T., Schumacker P.T. Prolonged hypoxia increases ROS signaling and RhoA activation in pulmonary artery smooth muscle and endothelial cells. Antioxid. Redox Signal. 2010, 12:603-610.
25. Cinel I., Ark M., Dellinger P., Karabacak T., Tamer L., Cinel L., Michael P., Hussein S., Parrillo J.E., Kumar A., Kumar A. Involvement of Rho kinase (ROCK) in sepsis-induced acute lung injury. J. Thorac. Dis. 2012, 4:30-39.
26. + channels to RhoA/Rho kinase in pulmonary vasoconstriction. Cardiovasc. Res. 2005, 66:84-93.
27. Coleman M.L., Sahai E.A., Yeo M., Bosch M., Dewar A., Olson M.F. Membrane blebbing during apoptosis results from caspase-mediated activation of ROCK I. Nat. Cell Biol. 2001, 3:339-345.
28. Connolly M.J., Aaronson P.I. Key role of the RhoA/Rho kinase system in pulmonary hypertension. Pulm. Pharmacol. Ther. 2011, 24:1-14.
29. Crespin M., Vidal C., Picard F., Lacombe C., Fontenay M. Activation of PAK1/2 during the shedding of platelet microvesicles. Blood Coagul. Fibrinolysis 2009, 20:63-70.
30. Curtis A.M., Wilkinson P.F., Gui M., Gales T.L., Hu E., Edelberg J.M. p38 mitogen-activated protein kinase targets the production of proinflammatory endothelial microparticles. J. Thromb. Haemost. 2009, 7:701-709.
31. D'Amico G., Jones D.T., Nye E., Sapienza K., Ramjuan A.R., Reynolds L.E., Robinson S.D., Kostourou V., Martinez D., Aubyn D., Grose R., Thomas G.J., Spencer-Dene B., Zicha D., Davies D., Tybulewicz V., Hodivala-Dilke K.M. Regulation of lymphatic-blood vessel separation by endothelial Rac1. Development 2009, 136:4043-4053.
32. Dasgupta S.K., Le A., Chavakis T., Rumbaut R.E., Thiagarajan P. Developmental endothelial locus-1 (Del-1) mediates clearance of platelet microparticles by the endothelium. Circulation 2012, 125:1664-1672.
33. de Jesus Perez V.A., Alastalo T.P., Wu J.C., Axelrod J.D., Cooke J.P., Amieva M., Rabinovitch M. Bone morphogenetic protein 2 induces pulmonary angiogenesis via Wnt-β-catenin and Wnt-RhoA-Rac1 pathways. J. Cell Biol. 2009, 184:83-99.
34. de Jesus Perez V.A., Ali Z., Alastalo T.P., Ikeno F., Sawada H., Lai Y.J., Kleisli T., Spiekerkoetter E., Qu X., Rubinos L.H., Ashley E., Amieva M., Dedhar S., Rabinovitch M. BMP promotes motility and represses growth of smooth muscle cells by activation of tandem Wnt pathways. J. Cell Biol. 2011, 192:171-188.
35. Diebold I., Petry A., Djordjevic T., Belaiba R.S., Fineman J., Black S., Schreiber C., Fratz S., Hess J., Kietzmann T., Gorlach A. Reciprocal regulation of Rac1 and PAK-1 by HIF-1alpha: a positive-feedback loop promoting pulmonary vascular remodeling. Antioxid. Redox Signal. 2010, 13:399-412.
36. Djordjevic T., Hess J., Herkert O., Gorlach A., BelAiba R.S. Rac regulates thrombin-induced tissue factor expression in pulmonary artery smooth muscle cells involving the nuclear factor-kappaB pathway. Antioxid. Redox Signal. 2004, 6:713-720.
37. Fukumoto Y., Shimokawa H. Recent progress in the management of pulmonary hypertension. Circ. J. 2011, 75:1801-1810.
38. Ghofrani H.A., Morrell N.W., Hoeper M.M., Olschewski H., Peacock A.J., Barst R.J., Shapiro S., Golpon H., Toshner M., Grimminger F., Pascoe S. Imatinib in pulmonary arterial hypertension patients with inadequate response to established therapy. Am. J. Respir. Crit. Care Med. 2010, 182:1171-1177.
39. Gorbunov N.V., Atkins J.L., Gurusamy N., Pitt B.R. Iron-induced remodeling in cultured rat pulmonary artery endothelial cells. Biometals 2011, 25:203-217.
40. Gordon C., Gudi K., Krause A., Sackrowitz R., Harvey B.G., Strulovici-Barel Y., Mezey J.G., Crystal R.G. Circulating endothelial microparticles as a measure of early lung destruction in cigarette smokers. Am. J. Respir. Crit. Care Med. 2011, 184:224-232.
41. Gorovoy M., Neamu R., Niu J., Vogel S., Predescu D., Miyoshi J., Takai Y., Kini V., Mehta D., Malik A.B., Voyno-Yasenetskaya T. RhoGDI-1 modulation of the activity of monomeric RhoGTPase RhoA regulates endothelial barrier function in mouse lungs. Circ. Res. 2007, 101:50-58.
42. Guilluy C., Sauzeau V., Rolli-Derkinderen M., Guerin P., Sagan C., Pacaud P., Loirand G. Inhibition of RhoA/Rho kinase pathway is involved in the beneficial effect of sildenafil on pulmonary hypertension. Br. J. Pharmacol. 2005, 146:1010-1018.
43. Guilluy C., Rolli-Derkinderen M., Loufrani L., Bourge A., Henrion D., Sabourin L., Loirand G., Pacaud P. Ste20-related kinase SLK phosphorylates Ser188 of RhoA to induce vasodilation in response to angiotensin II Type 2 receptor activation. Circ. Res. 2008, 102:1265-1274.
44. Guilluy C., Eddahibi S., Agard C., Guignabert C., Izikki M., Tu L., Savale L., Humbert M., Fadel E., Adnot S., Loirand G., Pacaud P. RhoA and Rho kinase activation in human pulmonary hypertension: role of 5-HT signaling. Am. J. Respir. Crit. Care Med. 2009, 179:1151-1158.
45. Hall A. Rho GTPases and the actin cytoskeleton. Science 1998, 279:509-514.
46. Hall A., Lalli G. Rho and Ras GTPases in axon growth, guidance, and branching. Cold Spring Harb. Perspect. Biol. 2010, 2:a001818.
47. Hancock J.F., Magee A.I., Childs J.E., Marshall C.J. All ras proteins are polyisoprenylated but only some are palmitoylated. Cell 1989, 57:1167-1177.
48. Hassanain H.H., Gregg D., Marcelo M.L., Zweier J.L., Souza H.P., Selvakumar B., Ma Q., Moustafa-Bayoumi M., Binkley P.F., Flavahan N.A., Morris M., Dong C., Goldschmidt-Clermont P.J. Hypertension caused by transgenic overexpression of Rac1. Antioxid. Redox Signal. 2007, 9:91-100.
49. Heasman S.J., Ridley A.J. Multiple roles for RhoA during T cell transendothelial migration. Small GTPases 2008, 1:174-179.
50. Heo J., Raines K.W., Mocanu V., Campbell S.L. Redox regulation of RhoA. Biochemistry 2006, 45:14481-14489.
51. Higashi M., Shimokawa H., Hattori T., Hiroki J., Mukai Y., Morikawa K., Ichiki T., Takahashi S., Takeshita A. Long-term inhibition of Rho-kinase suppresses angiotensin II-induced cardiovascular hypertrophy in rats in vivo: effect on endothelial NAD(P)H oxidase system. Circ. Res. 2003, 93:767-775.
52. Hordijk P.L. Regulation of NADPH oxidases: the role of Rac proteins. Circ. Res. 2006, 98:453-462.
53. Huang M., Duhadaway J.B., Prendergast G.C., Laury-Kleintop L.D. RhoB regulates PDGFR-beta trafficking and signaling in vascular smooth muscle cells. Arterioscler. Thromb. Vasc. Biol. 2007, 27:2597-2605.
54. Huang M., Satchell L., Duhadaway J.B., Prendergast G.C., Laury-Kleintop L.D. RhoB links PDGF signaling to cell migration by coordinating activation and localization of Cdc42 and Rac. J. Cell. Biochem. 2011, 112:1572-1584.
55. Humbert M., Trembath R.C. Genetics of pulmonary hypertension: from bench to bedside. Eur. Respir. J. 2002, 20:741-749.
56. Jaffe A.B., Hall A. Rho GTPases: biochemistry and biology. Annu. Rev. Cell Dev. Biol. 2005, 21:247-269.
57. 2+ sensitization in pulmonary vascular smooth muscle following chronic hypoxia. Am. J. Physiol. Lung Cell. Mol. Physiol. 2008, 295:L515-L529.
58. Johnson J.A., Hemnes A.R., Perrien D.S., Schuster M., Robinson L.J., Gladson S., Loibner H., Bai S., Blackwell T.R., Tada Y., Harral J.W., Talati M., Lane K.B., Fagan K.A., West J. Cytoskeletal defects in Bmpr2-associated pulmonary arterial hypertension. Am. J. Physiol. Lung Cell. Mol. Physiol. 2011, 302:L474-L484.
59. Kajimoto H., Hashimoto K., Bonnet S.N., Haromy A., Harry G., Moudgil R., Nakanishi T., Rebeyka I., Thebaud B., Michelakis E.D., Archer S.L. Oxygen activates the Rho/Rho-kinase pathway and induces RhoB and ROCK-1 expression in human and rabbit ductus arteriosus by increasing mitochondria-derived reactive oxygen species: a newly recognized mechanism for sustaining ductal constriction. Circulation 2007, 115:1777-1788.
60. Knock G.A., Snetkov V.A., Shaifta Y., Drndarski S., Ward J.P., Aaronson P.I. Role of src-family kinases in hypoxic vasoconstriction of rat pulmonary artery. Cardiovasc. Res. 2008, 80:453-462.
61. Lang P., Gesbert F., DelespineCarmagnat M., Stancou R., Pouchelet M., Bertoglio J. Protein kinase A phosphorylation of RhoA mediates the morphological and functional effects of cyclic AMP in cytotoxic lymphocytes. EMBO J. 1996, 15:510-519.
62. Lau W.K.W., Chan-Yeung M.M.W., Yip B.H.K., Cheung A.H.K., Ip M.S.M., et al. The role of circulating serotonin in the development of chronic obstructive pulmonary disease. PLoS One 2012, 7:e31617. 10.1371/journal.pone.0031617.
63. Laufs U., Liao J.K. Direct vascular effects of HMG-CoA reductase inhibitors. Trends Cardiovasc. Med. 2000, 10:143-148.
64. Laumanns I.P., Fink L., Wilhelm J., Wolff J.C., Mitnacht-Kraus R., Graef-Hoechst S., Stein M.M., Bohle R.M., Klepetko W., Hoda M.A., Schermuly R.T., Grimminger F., Seeger W., Voswinckel R. The noncanonical WNT pathway is operative in idiopathic pulmonary arterial hypertension. Am. J. Respir. Cell Mol. Biol. 2009, 40:683-691.
65. Leroyer A.S., Isobe H., Leseche G., Castier Y., Wassef M., Mallat Z., Binder B.R., Tedgui A., Boulanger C.M. Cellular origins and thrombogenic activity of microparticles isolated from human atherosclerotic plaques. J. Am. Coll. Cardiol. 2007, 49:772-777.
66. Leroyer A.S., Anfosso F., Lacroix R., Sabatier F., Simoncini S., Njock S.M., Jourde N., Brunet P., Camoin-Jau L., Sampol J., Dignat-George F. Endothelial-derived microparticles: biological conveyors at the crossroad of inflammation, thrombosis and angiogenesis. Thromb. Haemost. 2010, 104:456-463.
67. Li F.H., Xia W., Li A.W., Zhao C.F., Sun R.P. Inhibition of rho kinase attenuates high flow induced pulmonary hypertension in rats. Chin. Med. J. (Engl). 2007, 120:22-29.
68. Liu A., Du W., Liu J.P., Jessell T.M., Prendergast G.C. RhoB alteration is necessary for apoptotic and antineoplastic responses to farnesyltransferase inhibitors. Mol. Cell. Biol. 2000, 20:6105-6113.
69. Liu S., Kapoor M., Shi-wen X., Kennedy L., Denton C.P., Glogauer M., Abraham D.J., Leask A. Role of Rac1 in a bleomycin-induced scleroderma model using fibroblast-specific Rac1-knockout mice. Arthritis Rheum. 2008, 58:2189-2195.
70. Loirand G., Pacaud P. The role of Rho protein signaling in hypertension. Nat. Rev. Cardiol. 2010, 7:637-647.
71. Loirand G., Guilluy C., Pacaud P. Regulation of Rho proteins by phosphorylation in the cardiovascular system. Trends Cardiovasc. Med. 2006, 16:199-204.
72. Lu Q., Sakhatskyy P., Grinnell K., Newton J., Ortiz M., Wang Y., Sanchez-Esteban J., Harrington E.O., Rounds S. Cigarette smoke causes lung vascular barrier dysfunction via oxidative stress-mediated inhibition of RhoA and focal adhesion kinase. Am. J. Physiol. Lung Cell. Mol. Physiol. 2011, 301:L847-L857.
73. Machado R.D., Pauciulo M.W., Thomson J.R., Lane K.B., Morgan N.V., Wheeler L., Phillips J.A., Newman J., Williams D., Galie N., Manes A., McNeil K., Yacoub M., Mikhail G., Rogers P., Corris P., Humbert M., Donnai D., Martensson G., Tranebjaerg L., Loyd J.E., Trembath R.C., Nichols W.C. BMPR2 haploinsufficiency as the inherited molecular mechanism for primary pulmonary hypertension. Am. J. Hum. Genet. 2001, 68:92-102.
74. Mack C.P., Somlyo A.V., Hautmann M., Somlyo A.P., Owens G.K. Smooth muscle differentiation marker gene expression is regulated by RhoA-mediated actin polymerization. J. Biol. Chem. 2001, 276:341-347.
75. Maniatis N.A., Orfanos S.E. The endothelium in acute lung injury/acute respiratory distress syndrome. Curr. Opin. Crit. Care 2008, 14:22-30.
76. Martinez M.C., Tual-Chalot S., Leonetti D., Andriantsitohaina R. Microparticles: targets and tools in cardiovascular disease. Trends Pharmacol. Sci. 2011, 32:659-665.
77. McVey M.J., Tabuchi A., Kuebler W.M. Microparticles and acute lung injury. Am. J. Physiol. Lung Cell. Mol. Physiol. 2012, 10.1152/ajplung.00354.2011.
78. Milara J., Ortiz J.L., Juan G., Guijarro R., Almudever P., Martorell M., Morcillo E.J., Cortijo J. Cigarette smoke exposure up-regulates endothelin receptor B in human pulmonary artery endothelial cells: molecular and functional consequences. Br. J. Pharmacol. 2010, 161:1599-1615.
79. Millatt L.J., Whitley G.S., Li D.C., Leiper J.M., Siragy H.M., Carey R.M., Johns R.A. Evidence for dysregulation of dimethylarginine dimethylaminohydrolase I in chronic hypoxia-induced pulmonary hypertension. Circulation 2003, 108:1493-1498.
80. Mittelbrunn M., Sanchez-Madrid F. Intercellular communication: diverse structures for exchange of genetic information. Nat. Rev. Mol. Cell Biol. 2012, 13:328-335.
81. Morrell N.W. Role of bone morphogenetic protein receptors in the development of pulmonary arterial hypertension. Adv. Exp. Med. Biol. 2010, 661:251-264.
82. Nimnual A.S., Taylor L.J., Bar-Sagi D. Redox-dependent downregulation of Rho by Rac. Nat. Cell Biol. 2003, 5:236-241.
83. Nobes C.D., Hall A. Rho, Rac, and Cdc42 GTPases regulate the assembly of multimolecular focal complexes associated with actin stress fibers, lamellipodia, and filopodia. Cell 1995, 81:53-62.
84. Oka M., Fagan K.A., Jones P.L., McMurtry I.F. Therapeutic potential of RhoA/Rho kinase inhibitors in pulmonary hypertension. Br. J. Pharmacol. 2008, 155:444-454.
85. Parikh V.N., Jin R.C., Rabello S., Gulbahce N., White K., Hale A., Cottrill K.A., Shaik R.S., Waxman A.B., Zhang Y.Y., Maron B.A., Hartner J.C., Fujiwara Y., Orkin S.H., Haley K.J., Barabasi A.L., Loscalzo J., Chan S.Y. MicroRNA-21 integrates pathogenic signaling to control pulmonary hypertension: results of a network bioinformatics approach. Circulation 2012, 125:1520-1532.
86. Pedersen E., Brakebusch C. Rho GTPase function in development: how in vivo models change our view. Exp. Cell Res. 2012, 318:1779-1787.
87. Peinado V.I., Pizarro S., Barbera J.A. Pulmonary vascular involvement in COPD. Chest 2008, 134:808-814.
88. Prendergast G.C. Actin' up: RhoB in cancer and apoptosis. Nat. Rev. Cancer 2001, 1:162-168.
89. Prendergast G.C., Khosravi-Far R., Solski P.A., Kurzawa H., Lebowitz P.F., Der C.J. Critical role of Rho in cell transformation by oncogenic Ras. Oncogene 1995, 10:2289-2296.
90. Ramchandran R., Mehta D., Vogel S.M., Mirza M.K., Kouklis P., Malik A.B. Critical role of Cdc42 in mediating endothelial barrier protection in vivo. Am. J. Physiol. Lung Cell. Mol. Physiol. 2008, 295:L363-L369.
91. Rautou P.E., Vion A.C., Amabile N., Chironi G., Simon A., Tedgui A., Boulanger C.M. Microparticles, vascular function, and atherothrombosis. Circ. Res. 2011, 109:593-606.
92. Ridley A.J. Rho GTPases and cell migration. J. Cell Sci. 2001, 114:2713-2722.
93. Rodriguez P.L., Sahay S., Olabisi O.O., Whitehead I.P. ROCK I-mediated activation of NF-kappaB by RhoB. Cell. Signal. 2007, 19:2361-2369.
94. Rolli-Derkinderen M., Sauzeau V., Boyer L., Lemichez E., Baron C., Henrion D., Loirand G., Pacaud P. Phosphorylation of serine 188 protects RhoA from ubiquitin/proteasome-mediated degradation in vascular smooth muscle cells. Circ. Res. 2005, 96:1152-1160.
95. Rolli-Derkinderen M., Toumaniantz G., Pacaud P., Loirand G. RhoA phosphorylation induces Rac1 release from guanine dissociation inhibitor alpha and stimulation of vascular smooth muscle cell migration. Mol. Cell. Biol. 2010, 30:4786-4796.
96. Rupérez M., Rodrigues-Díez R., Blanco-Colio L.M., Sánchez-López E., Rodríguez-Vita J., Esteban V., Carvajal G., Plaza J.J., Egido J., Ruiz-Ortega M. HMG-CoA reductase inhibitors decrease angiotensin II-induced vascular fibrosis: role of RhoA/ROCK and MAPK pathways. Hypertension 2007, 50:377-383.
97. Sakai H., Fujita A., Watanabe A., Chiba Y., Kamei J., Misawa M. Different effects of smoke from heavy and light cigarettes on the induction of bronchial smooth muscle hyperresponsiveness in rats. J. Smooth Muscle Res. 2011, 47:1-10.
98. Sapet C., Simoncini S., Loriod B., Puthier D., Sampol J., Nguyen C., Dignat-George F., Anfosso F. Thrombin-induced endothelial microparticle generation: identification of a novel pathway involving ROCK-II activation by caspase-2. Blood 2006, 108:1868-1876.
99. 2+ sensitization of contraction in vascular smooth muscle. J. Biol. Chem. 2000, 275:21722-21729.
100. Sauzeau V., Rolli-Derkinderen M., Marionneau C., Loirand G., Pacaud P. RhoA expression is controlled by nitric oxide through cGMP-dependent protein kinase activation. J. Biol. Chem. 2003, 278:9472-9480.
101. Sawada N., Salomone S., Kim H.H., Kwiatkowski D.J., Liao J.K. Regulation of endothelial nitric oxide synthase and postnatal angiogenesis by Rac1. Circ. Res. 2008, 103:360-368.
102. Schermuly R.T., Ghofrani H.A., Wilkins M.R., Grimminger F. Mechanisms of disease: pulmonary arterial hypertension. Nat. Rev. Cardiol. 2011, 8:443-455.
103. Shibata R., Kai H., Seki Y., Kusaba K., Takemiya K., Koga M., Jalalidin A., Tokuda K., Tahara N., Niiyama H., Nagata T., Kuwahara F., Imaizumi T. Rho-kinase inhibition reduces neointima formation after vascular injury by enhancing Bax expression and apoptosis. J. Cardiovasc. Pharmacol. 2003, 42(Suppl. 1):S43-S47.
104. 2+ sensitivity of smooth muscle and nonmuscle myosin II: modulated by G proteins, kinases, and myosin phosphatase. Physiol. Rev. 2003, 83:1325-1358.
105. Spiekerkoetter E., Guignabert C., de Jesus Perez V., Alastalo T.P., Powers, Wang L., Lawrie A., Ambartsumian N., Schmidt A.M., Berryman M., Ashley R.H., Rabinovitch M. S100A4 and bone morphogenetic protein-2 codependently induce vascular smooth muscle cell migration via phospho-extracellular signal-regulated kinase and chloride intracellular channel 4. Circ. Res. 2009, 105:639-647.
106. Spindler V., Schlegel N., Waschke J. Role of GTPases in control of microvascular permeability. Cardiovasc. Res. 2010, 87:243-253.
107. Takahashi T., Kobayashi S., Fujino N., Suzuki T., Ota C., He M., Yamada M., Suzuki S., Yanai M., Kurosawa S., Yamaya M., Kubo H. Increased circulating endothelial microparticles in COPD patients: a potential biomarker for COPD exacerbation susceptibility. Thorax 2012, 10.1136/thoraxjnl-2011-201395.
108. Takemoto M., Sun J., Hiroki J., Shimokawa H., Liao J.K. Rho-kinase mediates hypoxia-induced downregulation of endothelial nitric oxide synthase. Circulation 2002, 106:57-62.
109. Toba M., Nagaoka T., Morio Y., Sato K., Uchida K., Homma N., Takahashi K. Involvement of Rho kinase in the pathogenesis of acute pulmonary embolism-induced polystyrene microspheres in rats. Am. J. Physiol. Lung Cell. Mol. Physiol. 2010, 298:L297-L303.
110. Trang P., Wiggins J.F., Daige C.L., Cho C., Omotola M., Brown D., Weidhaas J.B., Bader A.G., Slack F.J. Systemic delivery of tumor suppressor microRNA mimics using a neutral lipid emulsion inhibits lung tumors in mice. Mol. Ther. 2011, 19:1116-1122.
111. Tual-Chalot S., Guibert C., Muller B., Savineau J.P., Andriantsitohaina R., Martinez M.C. Circulating microparticles from pulmonary hypertensive rats induce endothelial dysfunction. Am. J. Respir. Crit. Care Med. 2010, 182:261-268.
112. Tung J.J., Hobert O., Berryman M., Kitajewski J. Chloride intracellular channel 4 is involved in endothelial proliferation and morphogenesis in vitro. Angiogenesis 2009, 12:209-220.
113. Turner S.J., Zhuang S., Zhang T., Boss G.R., Pilz R.B. Effects of lovastatin on Rho isoform expression, activity, and association with guanine nucleotide dissociation inhibitors. Biochem. Pharmacol. 2008, 75:405-413.
114. Ushio-Fukai M., Zafari A.M., Fukui T., Ishizaka N., Griendling K.K. p22phox is a critical component of the superoxide-generating NADH/NADPH oxidase system and regulates angiotensin II-induced hypertrophy in vascular smooth muscle cells. J. Biol. Chem. 1996, 271:23317-23321.
115. van der Heijden M., van Nieuw Amerongen G.P., van Bezu J., Paul M.A., Groeneveld A.B., van Hinsbergh V.W. Opposing effects of the angiopoietins on the thrombin-induced permeability of human pulmonary microvascular endothelial cells. PLoS One 2011, 6:e23448.
116. van Nieuw Amerongen G.P., Beckers C.M., Achekar I.D., Zeeman S., Musters R.J., van Hinsbergh V.W. Involvement of Rho kinase in endothelial barrier maintenance. Arterioscler. Thromb. Vasc. Biol. 2007, 27:2332-2339.
117. Vardouli L., Vasilaki E., Papadimitriou E., Kardassis D., Stournaras C. A novel mechanism of TGFbeta-induced actin reorganization mediated by Smad proteins and Rho GTPases. FEBS J. 2008, 275:4074-4087.
118. Vega F.M., Ridley A.J. Rho GTPases in cancer cell biology. FEBS Lett. 2008, 582:2093-2101.
119. Von Zee C.L., Stubbs E.B. Geranylgeranylation facilitates proteasomal degradation of Rho G-proteins in human trabecular meshwork cells. Invest. Ophthalmol. Vis. Sci. 2011, 52:1676-1683.
120. Von Zee C.L., Richards M.P., Bu P., Perlman J.I., Stubbs E.B. Increased RhoA and RhoB protein accumulation in cultured human trabecular meshwork cells by lovastatin. Invest. Ophthalmol. Vis. Sci. 2009, 50:2816-2823.
121. Wang Z., Jin N., Ganguli S., Swartz D.R., Li L., Rhoades R.A. Rho-kinase activation is involved in hypoxia-induced pulmonary vasoconstriction. Am. J. Respir. Cell Mol. Biol. 2001, 25:628-635.
122. Wherlock M., Gampel A., Futter C., Mellor H. Farnesyltransferase inhibitors disrupt EGF receptor traffic through modulation of the RhoB GTPase. J. Cell Sci. 2004, 117:3221-3231.
123. Wiggins J.F., Ruffino L., Kelnar K., Omotola M., Patrawala L., Brown D., Bader A.G. Development of a lung cancer therapeutic based on the tumor suppressor microRNA-34. Cancer Res. 2010, 70:5923-5930.
124. Wilkins M.R., Ali O., Bradlow W., Wharton J., Taegtmeyer A., Rhodes C.J., Ghofrani H.A., Howard L., Nihoyannopoulos P., Mohiaddin R.H., Gibbs J.S.R. Simvastatin as a treatment for pulmonary hypertension trial. Am. J. Respir. Crit. Care Med. 2010, 181:1106-1113.
125. Wojciak-Stothard B. New drug targets for pulmonary hypertension: Rho GTPases in pulmonary vascular remodelling. Postgrad. Med. J. 2008, 84:348-353.
126. Wojciak-Stothard B., Ridley A.J. Rho GTPases and the regulation of endothelial permeability. Vasc. Pharmacol. 2002, 39:187-199.
127. Wojciak-Stothard B., Tsang L.Y., Haworth S.G. Rac and Rho play opposing roles in the regulation of hypoxia/reoxygenation-induced permeability changes in pulmonary artery endothelial cells. Am. J. Physiol. Lung Cell. Mol. Physiol. 2005, 288:L749-L760.
128. Wojciak-Stothard B., Torondel B., Tsang L.Y., Fleming I., Fisslthaler B., Leiper J.M., Vallance P. The ADMA/DDAH pathway is a critical regulator of endothelial cell motility. J. Cell Sci. 2007, 120:929-942.
129. Wojciak-Stothard B., Torondel B., Zhao L., Renne T., Leiper J.M. Modulation of Rac1 activity by ADMA/DDAH regulates pulmonary endothelial barrier function. Mol. Biol. Cell 2009, 20:33-42.
130. Wojciak-Stothard B., Zhao L., Oliver E., Dubois O., Wu Y., Kardassis D., Vasilaki E., Huang M., Mitchell J.A., Louise H., Prendergast G.C., Wilkins M.R. Role of RhoB in the regulation of pulmonary endothelial and smooth muscle cell responses to hypoxia. Circ. Res. 2012, 110:1423-1434.
131. Wung B.S., Ni C.W., Wang D.L. ICAM-1 induction by TNFalpha and IL-6 is mediated by distinct pathways via Rac in endothelial cells. J. Biomed. Sci. 2005, 12:91-101.
132. Zampetaki A., Zhang Z., Hu Y., Xu Q. Biomechanical stress induces IL-6 expression in smooth muscle cells via Ras/Rac1-p38 MAPK-NF-kappaB signaling pathways. Am. J. Physiol. Heart Circ. Physiol. 2005, 288:H2946-H2954.
133. Zeng W.J., Xiong C.M., Zhao L., Shan G.L., Liu Z.H., Xue F., Gu Q., Ni X.H., Zhao Z.H., Cheng X.S., Wilkins M.R., He J.G. Atorvastatin in pulmonary arterial hypertension (APATH) study. Eur. Respir. J. 2012, 40:67-74.
134. Zhao L., Sebkhi A., Ali O., Wojciak-Stothard B., Mamanova L., Yang Q., Wharton J., Wilkins M.R. Simvastatin and sildenafil combine to attenuate pulmonary hypertension. Eur. Respir. J. 2009, 34:948-957.