Inhibition of phosphatidylinositol 3-kinase/akt signaling attenuates hypoxia-induced pulmonary artery remodeling and suppresses CREB depletion in arterial smooth muscle cells

Journal of Cardiovascular Pharmacology

Volumn 62, Issue 6, 2013, Pages 539-548

  Garat, Chrystelle V ^a   Crossno, Joseph T ^a   Sullivan, Timothy M ^a   Reusch, Jane E B ^a,b   Klemm, Dwight J ^a  

^a UNIVERSITY OF COLORADO   (United States)

^b VETERANS AFFAIRS MEDICAL CENTER   (United States)

Author keywords

Akt; CREB; Hypoxia; Phosphatidylinositol 3 kinase; Pulmonary arterial hypertension; Smooth muscle cell

Indexed keywords

COLLAGEN; CYCLIC AMP RESPONSIVE ELEMENT BINDING PROTEIN; FASUDIL; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN KINASE B;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTERIOLE; ARTERY MUSCLE; ARTICLE; CELL METABOLISM; CELL PROLIFERATION; CONTROLLED STUDY; EXTRACELLULAR MATRIX; HEART RIGHT VENTRICLE HYPERTROPHY; HYPOXIA; LUNG ARTERY PRESSURE; LUNG RESISTANCE; MALE; NONHUMAN; PRIORITY JOURNAL; PROTEIN DEPLETION; PROTEIN PHOSPHORYLATION; PULMONARY ARTERY; PULMONARY HYPERTENSION; RAT; SIGNAL TRANSDUCTION; SMOOTH MUSCLE FIBER;

ANIMALS; ANOXIA; ARTERIOLES; CELL PROLIFERATION; CYCLIC AMP RESPONSE ELEMENT-BINDING PROTEIN; ENZYME INHIBITORS; EXTRACELLULAR MATRIX; HYPERTENSION, PULMONARY; HYPERTROPHY, RIGHT VENTRICULAR; MALE; MUSCLE, SMOOTH, VASCULAR; PHOSPHATIDYLINOSITOL 3-KINASE; PROTEIN KINASE INHIBITORS; PROTEIN STABILITY; PROTO-ONCOGENE PROTEINS C-AKT; PULMONARY ARTERY; PULMONARY CIRCULATION; RATS; RATS, INBRED WKY; RHO-ASSOCIATED KINASES; SIGNAL TRANSDUCTION; VASODILATOR AGENTS;

EID: 84890572439     PISSN: 01602446     EISSN: 15334023     Source Type: Journal    
DOI: 10.1097/FJC.0000000000000014     Document Type: Article

References (43)

1. Rabinovitch M. Molecular pathogenesis of pulmonary arterial hypertension. J Clin Invest. 2012;122: 4306-4313.
2. Howell K, Preston RJ, McLoughlin P. Chronic hypoxia causes angiogenesis in addition to remodeling in the adult rat pulmonary circulation. J Physiol. 2003;547: 133-145.
3. Hsueh WA, Law RE. PPARg and atherosclerosis: effects on cell growth and movement. Arterioscler Thromb Vasc Biol. 2001;21: 1891-1895.
4. Hyvelin JM, Howell K, Nichol A, et al. Inhibition of Rho kinase attenuates hypoxia-induced angiogenesis in the pulmonary circulation. Circ Res. 2005;97: 185-191.
5. Dawes KE, Peacock AJ, Gray AJ, et al. Characterization of fibroblast mitogens and chemoattractants produced by endothelial cells exposed to hypoxia. Am J Respir Cell Mol Biol. 1994;10: 552-559.
6. Faller DV. Endothelial cell responses to hypoxic stress. Clinical and experimental pharmacology and physiology. Clin Exp Pharmacol Physiol. 1999;26: 74-84.
7. Pfeifer M, Blumberg FC, Wolf K, et al. Vascular remodeling and growth factor gene expression in the rat lung during hypoxia. Respir Physiol. 1998;111: 201-212.
8. Bornfeldt KE, Campbell JS, Koyama H, et al. The mitogen-activated protein kinase pathway can mediate growth inhibition and proliferation in smooth muscle cells. Dependence on the availability of downstream targets. J Clin Invest. 1997;100: 875-885.
9. Bornfeldt KE, Krebs EG. Crosstalk between protein kinase A and growth factor receptor signaling pathways in arterial smooth muscle cells. Cell Signal. 1999;11: 465-477.
10. Newby AC, Zaltsman AB. Molecular mechanisms in intimal hyperplasia. J Pathol. 2000;190: 300-309.
11. Rothman A, Wolner B, Button D, et al. Immediate-early gene expression in response to hypertrophic and proliferative stimuli in pulmonary arterial smooth muscle cells. J Biol Chem. 1994;269: 6399-6404.
12. Seasholtz TM, Majumdar M, Brown JH. Rho and Rho kinase mediate thrombin-stimulated vascular smooth muscle cell DNA synthesis and migration. Circ Res. 1999;84: 1186-1193.
13. Seasholtz TM, Zhang T, Morissette MR, et al. Increased expression and activity of RhoA are associated with increased DNA synthesis and reduced p27(Kip1) expression in the vasculature of hypertensive rats. Circ Res. 2001;89: 488-495.
14. Saward L, Zahradka P. Angiotensin II activates phosphatidylinositol 3-kinase in vascular smooth muscle cells. Circ Res. 1997;81: 249-257.
15. Gao BB, Hansen H, Chen HC, et al. Angiotensin II stimulates phosphorylation of an ectodomain-truncated platelet-derived growth factor receptor-beta and its binding to class IA PI3K in vascular smooth muscle cells. Biochem J. 2006;397: 337-344.
16. Jia G, Mitra AK, Gangahar DM, et al. Insulin-like growth factor-1 induces phosphorylation of PI3K-Akt/PKB to potentiate proliferation of smooth muscle cells in human saphenous vein. Exp Mol Pathol. 2010;89: 20-26.
17. Myit S, Delafontaine P, Bochaton-Piallat ML, et al. Different growth properties of neointimal and medial smooth muscle cells in response to growth factors. J Vasc Res. 2003;40: 97-104.
18. Heldin CH, Ostman A, Ronnstrand L. Signal transduction via plateletderived growth factor receptors. Biochim Biophys Acta. 1998;1378: F79-F113.
19. Goncharova EA, Ammit AJ, Irani C, et al. PI3K is required for proliferation and migration of human pulmonary vascular smooth muscle cells. Am J Physiol Lung Cell Mol Physiol. 2002;283:L354-L363.
20. Ivey ME, Osman N, Little PJ. Endothelin-1 signalling in vascular smooth muscle: pathways controlling cellular functions associated with atherosclerosis. Atherosclerosis. 2008;199: 237-247.
21. Graupera M, Guillermet-Guibert J, Foukas LC, et al. Angiogenesis selectively requires the p110alpha isoform of PI3K to control endothelial cell migration. Nature. 2008;453: 662-666.
22. Wang F, Yamauchi M, Muramatsu M, et al. RACK1 regulates VEGF/ Flt1-mediated cell migration via activation of a PI3K/Akt pathway. J Biol Chem. 2011;286: 9097-9106.
23. Weylie B, Zhu J, Singh U, et al. Phosphatidylinositide 3-kinase is important in late stage fibroblast growth factor-1-mediated angiogenesis in vivo. J Vasc Res. 2006;43: 61-69.
24. Nakao T, Shiota M, Tatemoto Y, et al. Pravastatin induces rat aortic endothelial cell proliferation and migration via activation of PI3K/Akt/mTOR/p70 S6 kinase signaling. J Pharmacol Sci. 2007;105: 334-341.
25. Chen J, Somanath PR, Razorenova O, et al. Akt1 regulates pathological angiogenesis, vascular maturation and permeability in vivo. Nat Med. 2005;11: 1188-1196.
26. Hamada K, Sasaki T, Koni PA, et al. The PTEN/PI3K pathways governs normal vascular development and tumor angiogenesis. Genes Dev. 2005; 19: 2054-2065.
27. Furgeson SB, Simpson PA, Park I, et al. Inactivation of the tumour suppressor, PTEN, in smooth muscle promotes a pro-inflammatory phenotype and enhances neointima formation. Cardiovasc Res. 2010;86: 274-282.
28. Klemm DJ, Watson P, Frid MG, et al. cAMP response element-binding protein content is a molecular determinant of smooth muscle cell proliferation and migration. J Biol Chem. 2001;276: 46132-46141.
29. Garat CV, Fankell D, Erickson PF, et al. Platelet-derived growth factor BB induces nuclear export and proteasomal degradation of CREB via phosphatidylinositol 3-kinase/Akt signaling in pulmonary artery smooth muscle cells. Mol Cell Biol. 2006;26: 4934-4948.
30. Vlahos CJ, Matter WF, Hui KY, et al. A specific inhibitor of phosphatidylinositol 3-kinase, 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4- one (LY294002). J Biol Chem. 1994;269: 5241-5248.
31. Hu L, Zaloudek C, Mills GB, et al. In vivo and in vitro ovarian carcinoma growth inhibition by a phosphatidylinositol 3-kinase inhibitor. Clin Cancer Res. 2000;6: 880-886.
32. Yang L, Dan HC, Sun M, et al. Akt/protein kinase B signaling inhibitor- 2, a selective small molecule inhibitor of Akt signaling with antitumor activity in cancer cells overexpressing Akt. Cancer Res. 2004;64:4394- 4399.
33. Karst AM, Dai DL, Cheng JQ, et al. Role of p53 up-regulated modulator of apoptosis and phosphorylated Akt in melanoma cell growth, apoptosis and patient survival. Cancer Res. 2006;66: 9221-9226.
34. Crossno JT Jr, Garat CV, Reusch JEB, et al. Rosiglitazone attenuates hypoxia-induced pulmonary arterial remodeling. Am J Physiol Lung Cell Mol Physiol. 2007;292:L885-L897.
35. Oka M, Morris KG, McMurtry IF. NIP-121 is more effective than nifedipine in acutely reversing chronic pulmonary hypertension. J Appl Physiol. 1993;75: 1075-1080.
36. Cross DA, Alessi DR, Cohen P, et al. Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B. Nature. 1995;378: 785-789.
37. Fagan KA, Oka M, Bauer NR, et al. Attenuation of acute hypoxic pulmonary vasoconstriction and hypoxic pulmonary hypertension in mice by inhibitors of Rho kinase. Am J Physiol Lung Cell Mol Physiol. 2004; 287:L656-L664.
38. Nagaoka T, Fagan KA, Gebb SA, et al. Inhaled Rho kinase inhibitors are potent and selective vasodilators in rat pulmonary hypertension. Am J Respir Crit Care Med. 2005;171: 494-499.
39. Klemm DJ, Majka SM, Crossno JT Jr, et al. Reduction of reactive oxygen species prevents hypoxia-induced CREB depletion in pulmonary artery smooth muscle cells. J Cardiovasc Pharmacol. 2011;58: 181-191.
40. Gary-Bobo G, Houssaini A, Amsellem V, et al. Effects of HIV protease inhibitors on progression of monocrotaline- and hypoxia-induced pulmonary hypertension in rats. Circulation. 2010;122: 1937-1947.
41. Karar J, Maity A. PI3/AKT/mTor pathway in angiogenesis. Front Mol Neurosci. 2011;4:51.
42. Gu T, Zhang Z, Wang J, et al. CREB is a novel nuclear target of PTEN phosphatase. Cancer Res. 2011;71: 2821-2825.
43. Clozel JP, Saunier C, Hartemann D, et al. Effects of cilazapril, a novel angiotensin converting enzyme inhibitor, on the structure of pulmonary arteries exposed to chronic hypoxia. J Cardiovasc Pharmacol. 1991;17: 36-40.