Sildenafil inhibits hypoxia-induced transient receptor potential canonical protein expression in pulmonary arterial smooth muscle via cGMP-PKG-PPAR γ axis

American Journal of Respiratory Cell and Molecular Biology

Volumn 49, Issue 2, 2013, Pages 231-240

  Wang, Jian ^a,c   Yang, Kai ^a,c   Xu, Lei ^a,c   Zhang, Yi ^c   Lai, Ning ^a,c   Jiang, Hua ^a   Zhang, Yajie ^b   Zhong, Nanshan ^a   Ran, Pixin ^a   Lu, Wenju ^a,b  

^a GUANGZHOU MEDICAL UNIVERSITY   (China)

^b GUANGZHOU MEDICAL UNIVERSITY   (China)

^c JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

PASMCs; PKG; PPAR ; Sildenafil; TRPC

Indexed keywords

2 CHLORO 5 NITRO N (4 PYRIDYL)BENZAMIDE; 8 (4 CHLOROPHENYLTHIO) GUANOSINE 3',5' CYCLIC MONOPHOSPHATE SODIUM SALT; CALCIUM ION; CYCLIC GMP; CYCLIC GMP DEPENDENT PROTEIN KINASE; KT 5823; MESSENGER RNA; N (2 BENZOYLPHENYL) O [2 (METHYL 2 PYRIDINYLAMINO)ETHYL]TYROSINE; OXYGEN; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA; PROTEIN; RP8 PROTEIN; SILDENAFIL; SMALL INTERFERING RNA; SODIUM; TRANSIENT RECEPTOR POTENTIAL CHANNEL 1; TRANSIENT RECEPTOR POTENTIAL CHANNEL 6; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTERY MUSCLE; ARTICLE; BIOLOGICAL ACTIVITY; CELL ACTIVITY; CELL CULTURE; CELL ISOLATION; CELL LEVEL; CELL MIGRATION; CELL PROLIFERATION; CONTROLLED STUDY; DRUG MECHANISM; FLUORESCENCE MICROSCOPY; GENE SILENCING; GENETIC TRANSFECTION; HEMODYNAMIC PARAMETERS; HISTOCHEMISTRY; HISTOPATHOLOGY; HYPOXIA; HYPOXIA INDUCED TRANSIENT RECEPTOR POTENTIAL CNONICAL PROTEIN EXPRESSION; HYPOXIC PULMONARY HYPERTENSION; MALE; MEASUREMENT; NONHUMAN; PROTEIN EXPRESSION; PROTEIN FUNCTION; PULMONARY ARTERY; PULMONARY HYPERTENSION; RAT; REAL TIME POLYMERASE CHAIN REACTION; RECEPTOR POTENTIAL; STORE OPERATED CALCIUM ION ENTRY; WESTERN BLOTTING;

ANIMALS; ANOXIA; BENZAMIDES; BENZOPHENONES; CARBAZOLES; CELL MOVEMENT; CELL PROLIFERATION; CYCLIC GMP; CYCLIC GMP-DEPENDENT PROTEIN KINASES; GENE EXPRESSION REGULATION; MALE; MUSCLE, SMOOTH, VASCULAR; MYOCYTES, SMOOTH MUSCLE; PHOSPHODIESTERASE 5 INHIBITORS; PIPERAZINES; PPAR GAMMA; PROTEIN KINASE INHIBITORS; PULMONARY ARTERY; PURINES; PYRIDINES; RATS; RATS, WISTAR; SIGNAL TRANSDUCTION; SULFONES; TRPC CATION CHANNELS; TYROSINE;

EID: 84883143411     PISSN: 10441549     EISSN: 15354989     Source Type: Journal    
DOI: 10.1165/rcmb.2012-0185OC     Document Type: Article

References (58)

1. Karaki H, Ozaki H, Hori M, Mitsui-Saito M, Amano K, Harada K, Miyamoto S, Nakazawa H, Won KJ, Sato K. Calcium movements, distribution, and functions in smooth muscle. Pharmacol Rev 1997; 49: 157-230.
2. Ward JP, Robertson TP, Aaronson PI. Capacitative calcium entry: a central role in hypoxic pulmonary vasoconstriction? Am J Physiol Lung Cell Mol Physiol 2005;289:L2-L4.
3. Remillard CV, Yuan JX. TRP channels, CCE, and the pulmonary vascular smooth muscle. Microcirculation 2006;13: 671-692.
4. Weigand L, Foxson J, Wang J, Shimoda LA, Sylvester JT. Inhibition of hypoxic pulmonary vasoconstriction by antagonists of store-operated Ca21 and nonselective cation channels. Am J Physiol Lung Cell Mol Physiol 2005;289:L5-L13.
5. Wang J, Weigand L, Lu W, Sylvester JT, Semenza GL, Shimoda LA. Hypoxia inducible factor 1 mediates hypoxia-induced TRPC expression and elevated intracellular Ca21 in pulmonary arterial smooth muscle cells. Circ Res 2006;98: 1528-1537.
6. Lin MJ, Leung GP, Zhang WM, Yang XR, Yip KP, Tse CM, Sham JS. Chronic hypoxia-induced upregulation of store-operated and receptor-operated Ca21 channels in pulmonary arterial smooth muscle cells: a novel mechanism of hypoxic pulmonary hypertension. Circ Res 2004;95: 496-505.
7. Wang J, Shimoda LA, Weigand L, Wang W, Sun D, Sylvester JT. Acute hypoxia increases intracellular [Ca21] in pulmonary arterial smooth muscle by enhancing capacitative Ca21 entry. Am J Physiol Lung Cell Mol Physiol 2005;288:L1059-L1069.
8. Wang J, Shimoda LA, Sylvester JT. Capacitative calcium entry and TRPC channel proteins are expressed in rat distal pulmonary arterial smooth muscle. Am J Physiol Lung Cell Mol Physiol 2004; 286:L848-L858.
9. Lu W, Wang J, Shimoda LA, Sylvester JT. Differences in STIM1 and TRPC expression in proximal and distal pulmonary arterial smooth muscle are associated with differences in Ca21 responses to hypoxia. Am J Physiol Lung Cell Mol Physiol 2008;295:L104-L113.
10. Lu W, Ran P, Zhang D, Peng G, Li B, Zhong N, Wang J. Sildenafil inhibits chronically hypoxic upregulation of canonical transient receptor potential expression in rat pulmonary arterial smooth muscle. Am J Physiol Cell Physiol 2010;298:C114-C123.
11. Savineau JP, Gonzalez De La Fuente P, Marthan R. Effect of vascular smooth muscle relaxants on the protein kinase C-mediated contraction in the rat pulmonary artery. Eur J Pharmacol 1993;249: 191-198.
12. Tantini B, Manes A, Fiumana E, Pignatti C, Guarnieri C, Zannoli R, Md AB, Galie N. Antiproliferative effect of sildenafil on human pulmonary artery smooth muscle cells. Basic Res Cardiol 2005;100: 131-138.
13. MacLean MR, Sweeney G, Baird M, McCulloch KM, Houslay M, Morecroft I. 5-hydroxytryptamine receptors mediating vasoconstriction in pulmonary arteries from control and pulmonary hypertensive rats. Br J Pharmacol 1996;119: 917-930.
14. Maclean MR, Johnston ED, McCulloch KM, Pooley L, Houslay MD, Sweeney G. Phosphodiesterase isoforms in the pulmonary arterial circulation of the rat: changes in pulmonary hypertension. J Pharmacol Exp Ther 1997;283: 619-624.
15. Chen IS, Dai ZK, Welsh DG, Chen IJ, Wu BN. Protein kinases modulate store-operated channels in pulmonary artery smooth muscle cells. J Biomed Sci 2011;18:2.
16. Ameshima S, Golpon H, Cool CD, Chan D, Vandivier RW, Gardai SJ, Wick M, Nemenoff RA, Geraci MW, Voelkel NF. Peroxisome proliferator-activated receptor gamma (PPARgamma) expression is decreased in pulmonary hypertension and affects endothelial cell growth. Circ Res 2003;92: 1162-1169.
17. Hansmann G, Wagner RA, Schellong S, Perez VA, Urashima T, Wang L, Sheikh AY, Suen RS, Stewart DJ, Rabinovitch M. Pulmonary arterial hypertension is linked to insulin resistance and reversed by peroxisome proliferator-activated receptor-gamma activation. Circulation 2007;115: 1275-1284.
18. Crossno JT Jr, Garat CV, Reusch JE, Morris KG, Dempsey EC, McMurtry IF, Stenmark KR, Klemm DJ. Rosiglitazone attenuates hypoxia-induced pulmonary arterial remodeling. Am J Physiol Lung Cell Mol Physiol 2007;292:L885-L897.
19. Matsuda Y, Hoshikawa Y, Ameshima S, Suzuki S, Okada Y, Tabata T, Sugawara T, Matsumura Y, Kondo T. Effects of peroxisome proliferator- activated receptor gamma ligands on monocrotaline-induced pulmonary hypertension in rats. Nihon Kokyuki Gakkai Zasshi 2005;43: 283-288.
20. Kim EK, Lee JH, Oh YM, Lee YS, Lee SD. Rosiglitazone attenuates hypoxia-induced pulmonary arterial hypertension in rats. Respirology 2010;15: 659-668.
21. Nisbet RE, Bland JM, Kleinhenz DJ,Mitchell PO, Walp ER, Sutliff RL, Hart CM. Rosiglitazone attenuates chronic hypoxia-induced pulmonary hypertension in a mouse model. Am J Respir Cell Mol Biol 2010;42: 482-490.
22. Hansmann G, de Jesus Perez VA, Alastalo TP, Alvira CM, Guignabert C, Bekker JM, Schellong S, Urashima T, Wang L, Morrell NW, et al. An antiproliferative BMP-2/PPARgamma/APoE axis in human and murine SMCs and its role in pulmonary hypertension. J Clin Invest 2008;118: 1846-1857.
23. Guignabert C, Alvira CM, Alastalo TP, Sawada H, Hansmann G, Zhao M, Wang L, El-Bizri N, Rabinovitch M. TIE2-mediated loss of peroxisome proliferator-activated receptor-gamma in mice causes PDGF receptor-beta- dependent pulmonary arterial muscularization. Am J Physiol Lung Cell Mol Physiol 2009;297:L1082-L1090.
24. Wang J, Jiang Q,Wan L, Yang K, Zhang Y, Chen Y,Wang E, Lai N, Zhao L, Jiang H, et al. Sodium tanshinone IIA sulfonate inhibits canonical transient receptor potential expression in pulmonary arterial smooth muscle from pulmonary hypertensive rats. Am J Respir Cell Mol Biol 2013;48: 125-134.
25. Butt E, Abel K, Krieger M, Palm D, Hoppe V, Hoppe J, Walter U. CAMP- and cGMP-dependent protein kinase phosphorylation sites of the focal adhesion vasodilator-stimulated phosphoprotein (VASP) in vitro and in intact human platelets. J Biol Chem 1994;269: 14509-14517.
26. Yu Y, Fantozzi I, Remillard CV, Landsberg JW, Kunichika N, Platoshyn O, Tigno DD, Thistlethwaite PA, Rubin LJ, Yuan JX. Enhanced expression of transient receptor potential channels in idiopathic pulmonary arterial hypertension. Proc Natl Acad Sci USA 2004;101: 13861-13866.
27. Liu XR, Zhang MF, Yang N, Liu Q,Wang RX, Cao YN, Yang XR, Sham JS, LinMJ. Enhanced store-operated Ca(2)1 entry and TRPC channel expression in pulmonary arteries of monocrotaline-induced pulmonary hypertensive rats. Am J Physiol Cell Physiol 2012;302:C77-C87.
28. Fuchs B, Dietrich A, Gudermann T, Kalwa H, Grimminger F, Weissmann N. The role of classical transient receptor potential channels in the regulation of hypoxic pulmonary vasoconstriction. Adv Exp Med Biol 2010;661: 187-200.
29. Yu Y, Keller SH, Remillard CV, Safrina O, Nicholson A, Zhang SL, Jiang W, Vangala N, Landsberg JW, Wang JY, et al. A functional single-nucleotide polymorphism in the TRPC6 gene promoter associated with idiopathic pulmonary arterial hypertension. Circulation 2009;119: 2313-2322.
30. Kunichika N, Yu Y, Remillard CV, Platoshyn O, Zhang S, Yuan JX. Overexpression of TRPC1 enhances pulmonary vasoconstriction induced by capacitative Ca21 entry. Am J Physiol Lung Cell Mol Physiol 2004;287: L962-L969.
31. Weigand LA, Wang J, Shimoda LA, Sham JSK, Sylvester JT. Inhibitors of capacitative calcium entry block hypoxic pulmonary vasoconstriction in isolated rat lungs. Am J Respir Crit CareMed 2003;167:A698 (abstract).
32. McDaniel SS, Platoshyn O, Wang J, Yu Y, SweeneyM, Krick S, Rubin LJ, Yuan JX. Capacitative Ca21 entry in agonist-induced pulmonary vasoconstriction. Am J Physiol Lung Cell Mol Physiol 2001;280:L870-L880.
33. Urban N, Hill K, Wang L, KueblerWM, Schaefer M. Novel pharmacological TRPC inhibitors block hypoxia-induced vasoconstriction. Cell Calcium 2012;51: 194-206.
34. Weissmann N, Dietrich A, Fuchs B, Kalwa H, Ay M, Dumitrascu R, Olschewski A, Storch U, Mederos y Schnitzler M, Ghofrani HA, et al. Classical transient receptor potential channel 6 (TRPC6) is essential for hypoxic pulmonary vasoconstriction and alveolar gas exchange. Proc Natl Acad Sci USA 2006;103: 19093-19098.
35. Yu Y, Sweeney M, Zhang S, Platoshyn O, Landsberg J, Rothman A, Yuan JX. PDGF stimulates pulmonary vascular smooth muscle cell proliferation by upregulating TRPC6 expression. Am J Physiol Cell Physiol 2003;284:C316-C330.
36. Sweeney M, Yu Y, Platoshyn O, Zhang S, McDaniel SS, Yuan JX. Inhibition of endogenous TRP1 decreases capacitative Ca21 entry and attenuates pulmonary artery smooth muscle cell proliferation. Am J Physiol Lung Cell Mol Physiol 2002;283:L144-L155.
37. Schlossmann J, Schinner E. cGMP becomes a drug target. Naunyn Schmiedebergs Arch Pharmacol (In press)
38. Schlossmann J, Ammendola A, Ashman K, Zong X, Huber A, Neubauer G, Wang GX, Allescher HD, Korth M, Wilm M, et al. Regulation of intracellular calcium by a signalling complex of IRAG, IP3 receptor and cGMP kinase Ibeta. Nature 2000;404: 197-201.
39. Morgado M, Cairrao E, Santos-Silva AJ, Verde I. Cyclic nucleotide- dependent relaxation pathways in vascular smooth muscle. Cell Mol Life Sci 2012;69: 247-266.
40. Jernigan NL, Resta TC. Chronic hypoxia attenuates cGMP-dependent pulmonary vasodilation. Am J Physiol Lung Cell Mol Physiol 2002; 282:L1366-L1375.
41. Zhou W, Dasgupta C, Negash S, Raj JU. Modulation of pulmonary vascular smooth muscle cell phenotype in hypoxia: role of cGMPdependent protein kinase. Am J Physiol Lung Cell Mol Physiol 2007;292:L1459-L1466.
42. Paria BC, Malik AB, Kwiatek AM, Rahman A, May MJ, Ghosh S, Tiruppathi C. Tumor necrosis factor-alpha induces nuclear factor- kappaB-dependent TRPC1 expression in endothelial cells. J Biol Chem 2003;278: 37195-37203.
43. Zhang H, Ding J, Fan Q, Liu S. TRPC6 up-regulation in ANG II-induced podocyte apoptosis might result from ERK activation and NF-kappaB translocation. Exp Biol Med (Maywood) 2009;234: 1029-1036.
44. El Hiani Y, Lehen'kyi V, Ouadid-Ahidouch H, Ahidouch A. Activation of the calcium-sensing receptor by high calcium induced breast cancer cell proliferation and TRPC1 cation channel over-expression potentially through EGFR pathways. Arch Biochem Biophys 2009;486: 58-63.
45. Takahashi S, Lin H, Geshi N, Mori Y, Kawarabayashi Y, Takami N, Mori MX, Honda A, Inoue R. Nitric oxide-CGMP-protein kinase G pathway negatively regulates vascular transient receptor potential channel TRPC6. J Physiol 2008;586: 4209-4223.
46. Koitabashi N, Aiba T, Hesketh GG, Rowell J, Zhang M, Takimoto E, Tomaselli GF, Kass DA. Cyclic GMP/PKG-dependent inhibition of TRPC6 channel activity and expression negatively regulates cardiomyocyte NFAT activation: novel mechanism of cardiac stress modulation by PDE5 inhibition. J Mol Cell Cardiol 2010;48: 713-724.
47. He W, Barak Y, Hevener A, Olson P, Liao D, Le J, Nelson M, Ong E, Olefsky JM, Evans RM. Adipose-specific peroxisome proliferator- activated receptor gamma knockout causes insulin resistance in fat and liver but not in muscle. Proc Natl Acad Sci USA 2003;100: 15712-15717.
48. Hevener AL, He W, Barak Y, Le J, Bandyopadhyay G, Olson P, Wilkes J, Evans RM, Olefsky J. Muscle-specific PPARG deletion causes insulin resistance. Nat Med 2003;9: 1491-1497.
49. Lehrke M, Lazar MA. The many faces of PPARgamma. Cell 2005;123: 993-999.
50. Gauthier A, Vassiliou G, Benoist F, McPherson R. Adipocyte low density lipoprotein receptor-related protein gene expression and function is regulated by peroxisome proliferator-activated receptor gamma. J Biol Chem 2003;278: 11945-11953.
51. Newton CS, Loukinova E, Mikhailenko I, Ranganathan S, Gao Y, Haudenschild C, Strickland DK. Platelet-derived growth factor receptor-beta (PDGFR-beta) activation promotes its association with the low density lipoprotein receptor-related protein (LRP): evidence for co-receptor function. J Biol Chem 2005;280: 27872-27878.
52. Vantler M, Caglayan E, Zimmermann WH, Baumer AT, Rosenkranz S. Systematic evaluation of anti-apoptotic growth factor signaling in vascular smooth muscle cells: only phosphatidylinositol 39 kinase is important. J Biol Chem 2005;280: 14168-14176.
53. Wakino S, Kintscher U, Kim S, Yin F, Hsueh WA, Law RE. Peroxisome proliferator-activated receptor gamma ligands inhibit retinoblastoma phosphorylation and G1 → S transition in vascular smooth muscle cells. J Biol Chem 2000;275: 22435-22441.
54. Cowan KN, Heilbut A, Humpl T, Lam C, Ito S, Rabinovitch M. Complete reversal of fatal pulmonary hypertension in rats by a serine elastase inhibitor. Nat Med 2000;6: 698-702.
55. Wakino S, Kanda T, Hayashi K. Rho/Rho kinase as a potential target for the treatment of renal disease. Drug News Perspect 2005;18: 639-643.
56. Worley JR, Baugh MD, Hughes DA, Edwards DR, Hogan A, Sampson MJ, Gavrilovic J. Metalloproteinase expression in PMA-stimulated THP-1 cells: effects of peroxisome proliferator-activated receptor- gamma (PPAR gamma) agonists and 9-cis-retinoic acid. J Biol Chem 2003;278: 51340-51346.
57. Hansmann G, Rabinovitch M. The protective role of adiponectin in pulmonary vascular disease. Am J Physiol Lung Cell Mol Physiol 2010;298:L1-L2.
58. Zhang X, Ji J, Yan G, Wu J, Sun X, Shen J, Jiang H, Wang H. Sildenafil promotes adipogenesis through a PKG pathway. Biochem Biophys Res Commun 2010;396: 1054-1059.