Table of Contents Author Guidelines Submit a Manuscript
Pulmonary Medicine
Volume 2011 (2011), Article ID 573432, 12 pages
http://dx.doi.org/10.1155/2011/573432
Review Article

Cell-Specific Dual Role of Caveolin-1 in Pulmonary Hypertension

Section of Pediatric Cardiology, Department of Physiology, New York Medical College, Valhalla, NY 10595, USA

Received 9 January 2011; Accepted 10 March 2011

Academic Editor: Andrew J. Halayko

Copyright © 2011 Rajamma Mathew. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. M. Humbert, O. Sitbon, A. Chaouat et al., “Pulmonary arterial hypertension in France: results from a national registry,” American Journal of Respiratory and Critical Care Medicine, vol. 173, no. 9, pp. 1023–1030, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  2. A. J. Peacock, N. F. Murphy, J. J. V. McMurrey, L. Caballero, and S. Stewart, “An epidemiological study of pulmonary arterial hypertension,” European Respiratory Journal, vol. 30, no. 1, pp. 104–109, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  3. G. Simonneau, I. M. Robbins, M. Beghetti et al., “Updated clinical classification of pulmonary hypertension,” Journal of the American College of Cardiology, vol. 54, no. 1, pp. S43–S54, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  4. S. Rich, D. R. Dantzker, S. M. Ayres et al., “Primary pulmonary hypertension. A national prospective study,” Annals of Internal Medicine, vol. 107, no. 2, pp. 216–223, 1987. View at Google Scholar · View at Scopus
  5. A. T. Dinh Xuan, T. W. Higenbottam, C. Clelland, J. Pepke-Zaba, G. Cremona, and J. Wallwork, “Impairment of pulmonary endothelium-dependent relaxation in patients with Eisenmenger's syndrome,” British Journal of Pharmacology, vol. 99, no. 1, pp. 9–10, 1990. View at Google Scholar · View at Scopus
  6. R. Mathew, E. S. Gloster, T. Sundararajan, C. I. Thompson, G. A. Zeballos, and M. H. Gewitz, “Role of inhibition of nitric oxide production in monocrotaline-induced pulmonary hypertension,” Journal of Applied Physiology, vol. 82, no. 5, pp. 1493–1498, 1997. View at Google Scholar · View at Scopus
  7. R. M. Tuder, C. D. Cool, M. W. Geraci et al., “Prostacyclin synthase expression is decreased in lungs from patients with severe pulmonary hypertension,” American Journal of Respiratory and Critical Care Medicine, vol. 159, no. 6, pp. 1925–1932, 1999. View at Google Scholar · View at Scopus
  8. A. Giaid, M. Yanagisawa, D. Langleben et al., “Expression of endothelin-1 in the lungs of patients with pulmonary hypertension,” The New England Journal of Medicine, vol. 328, no. 24, pp. 1732–1739, 1993. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  9. R. Mathew, G. A. Zeballos, H. Tun, and M. H. Gewitz, “Role of nitric oxide and endothelin-1 in monocrotaline-induced pulmonary hypertension in rats,” Cardiovascular Research, vol. 30, no. 5, pp. 739–746, 1995. View at Publisher · View at Google Scholar · View at Scopus
  10. R. T. Schermuly, E. Dony, H. A. Ghofrani et al., “Reversal of experimental pulmonary hypertension by PDGF inhibition,” Journal of Clinical Investigation, vol. 115, no. 10, pp. 2811–2821, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  11. R. Dumitrascu, C. Kulcke, M. Kongshoff et al., “Terguride ameliorates monocrotaline induced pulmonary hypertension in rats,” European Respiratory Journal, vol. 37, no. 5, pp. 1104–1118, 2011. View at Publisher · View at Google Scholar · View at PubMed
  12. M. S. McMurtry, S. L. Archer, D. C. Altieri et al., “Gene therapy targeting survivin selectively induces pulmonary vascular apoptosis and reverses pulmonary arterial hypertension,” Journal of Clinical Investigation, vol. 115, no. 6, pp. 1479–1491, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  13. J. F. Jasmin, I. Mercier, R. Hnasko et al., “Lung remodeling and pulmonary hypertension after myocardial infarction: pathogenic role of reduced caveolin expression,” Cardiovascular Research, vol. 63, no. 4, pp. 747–755, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  14. R. Mathew, J. Huang, M. Shah, K. Patel, M. Gewitz, and P. B. Sehgal, “Disruption of endothelial-cell caveolin-1α/raft scaffolding during development of monocrotaline-induced pulmonary hypertension,” Circulation, vol. 110, no. 11, pp. 1499–1506, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  15. F. A. Masri, W. Xu, S. A. A. Comhair et al., “Hyperproliferative apoptosis-resistant endothelial cells in idiopathic pulmonary arterial hypertension,” American Journal of Physiology, vol. 293, no. 3, pp. L548–L554, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  16. Z. Do.e Z., Y. Fukumoto, A. Takaki et al., “Evidence for Rho-kinase activation in patients with pulmonary arterial hypertension,” Circulation Journal, vol. 73, no. 9, pp. 1731–1739, 2009. View at Publisher · View at Google Scholar · View at Scopus
  17. M. Oka, K. A. Fagan, P. L. Jones, and I. F. McMurtry, “Therapeutic potential of RhoA/Rho kinase inhibitors in pulmonary hypertension,” British Journal of Pharmacology, vol. 155, no. 4, pp. 444–454, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  18. M. Lévy, C. Maurey, D. S. Celermajer et al., “Impaired apoptosis of pulmonary endothelial cells is associated with intimal proliferation and irreversibility of pulmonary hypertension in congenital heart disease,” Journal of the American College of Cardiology, vol. 49, no. 7, pp. 803–810, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  19. J. Huang, J. H. Wolk, M. H. Gewitz, and R. Mathew, “Progressive endothelial cell damage in an inflammatory model of pulmonary hypertension,” Experimental Lung Research, vol. 36, no. 1, pp. 57–66, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  20. C. Ye and M. Rabinovitch, “Inhibition of elastolysis by SC-37698 reduces development and progression of monocrotaline pulmonary hypertension,” American Journal of Physiology, vol. 261, no. 4, pp. H1255–H1267, 1991. View at Google Scholar · View at Scopus
  21. H. Lepetit, S. Eddahibi, E. Fadel et al., “Smooth muscle cell matrix metalloproteinases in idiopathic pulmonary arterial hypertension,” European Respiratory Journal, vol. 25, no. 5, pp. 834–842, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  22. J. R. Thomson, R. D. Machado, M. W. Pauciulo et al., “Sporadiac primary pulmonary hypertension is associated with germline mutations of the gene encoding BMPR-II, a receptor member of the TGF-β family,” Journal of Medical Genetics, vol. 37, no. 10, pp. 741–745, 2000. View at Google Scholar · View at Scopus
  23. R. D. Machado, M. A. Aldred, V. James et al., “Mutations of the TGF-β type II receptor BMPR2 in pulmonary arterial hypertension,” Human Mutation, vol. 27, no. 2, pp. 121–132, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  24. J. D. Cogan, M. W. Pauciulo, A. P. Batchman et al., “High frequency of BMPR2 exonic deletions/duplications in familial pulmonary arterial hypertension,” American Journal of Respiratory and Critical Care Medicine, vol. 174, no. 5, pp. 590–598, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  25. K. E. Roberts, J. J. McElroy, W. P. K. Wong et al., “BMPR2 mutations in pulmonary arterial hypertension with congenital heart disease,” European Respiratory Journal, vol. 24, no. 3, pp. 371–374, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  26. L. Long, A. Crosby, X. Yang et al., “Altered bone morphogenetic protein and transforming growth factor-β signaling in rat models of pulmonary hypertension. Potential for activin receptor-like kinase-5 inhibition in prevention and progression of disease,” Circulation, vol. 119, no. 4, pp. 566–576, 2009. View at Publisher · View at Google Scholar · View at PubMed
  27. K. Murakami, R. Mathew, J. Huang et al., “Smurf1 ubiquitin ligase causes downregulation of BMP receptors and is induced in monocrotaline and hypoxia models of pulmonary arterial hypertension,” Experimental Biology and Medicine, vol. 235, no. 7, pp. 805–813, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  28. R. C. Trembath, J. R. Thomson, R. D. Machado et al., “Clinical and molecular genetic features of pulmonary hypertension in patients with hereditary hemorrhagic telangiectasia,” The New England Journal of Medicine, vol. 345, no. 5, pp. 325–334, 2001. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  29. K. R. Stenmark and M. Rabinovitch, “Emerging therapies for the treatment of pulmonary hypertension,” Pediatric Critical Care Medicine, vol. 11, no. 2, pp. S85–S90, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  30. R. O. D. Achcar, Y. Demura, P. R. Rai et al., “Loss of caveolin and heme oxygenase expression in severe pulmonary hypertension,” Chest, vol. 129, no. 3, pp. 696–705, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  31. H. H. Patel, S. Zhang, F. Murray et al., “Increased smooth muscle cell expression of caveolin-1 and caveolae contribute to the pathophysiology of idiopathic pulmonary arterial hypertension,” The FASEB Journal, vol. 21, no. 11, pp. 2970–2979, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  32. R. Mathew, J. Huang, U. S. Katta, U. Krishnan, C. Sandoval, and M. H. Gewitz, “Immunosuppressant-induced endothelial damage and pulmonary arterial hypertension,” Journal of Pediatric Hematology/Oncology, vol. 33, no. 1, pp. 55–58, 2011. View at Publisher · View at Google Scholar · View at PubMed
  33. G. E. Palade, “Fine structure of blood capillaries,” Journal of Applied Physiology, vol. 24, pp. 1424–1436, 1953. View at Google Scholar
  34. E. Yamada, “The fine structure of the gall bladder epithelium of the mouse,” The Journal of Biophysical and Biochemical Cytology, vol. 1, no. 5, pp. 445–458, 1955. View at Google Scholar · View at Scopus
  35. T. M. Williams and M. P. Lisanti, “The caveolin proteins,” Genome Biology, vol. 5, no. 3, article 214, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  36. P. G. Frank, S. E. Woodman, D. S. Park, and M. P. Lisanti, “Caveolin, caveolae, and endothelial cell function,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 23, no. 7, pp. 1161–1168, 2003. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  37. B. Razani, S. E. Woodman, and M. P. Lisanti, “Caveolae: from cell biology to animal physiology,” Pharmacological Reviews, vol. 54, no. 3, pp. 431–467, 2002. View at Publisher · View at Google Scholar · View at Scopus
  38. P. Liu, M. Rudick, and R. G. W. Anderson, “Multiple functions of caveolin-1,” The Journal of Biological Chemistry, vol. 277, no. 44, pp. 41295–41298, 2002. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  39. A. F. G. Quest, L. Leyton, and M. Párraga, “Caveolins, caveolae, and lipid rafts in cellular transport, signaling, and disease,” Biochemistry and Cell Biology, vol. 82, no. 1, pp. 129–144, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  40. E. J. Smart, G. A. Graf, M. A. McNiven et al., “Caveolins, liquid-ordered domains, and signal transduction,” Molecular and Cellular Biology, vol. 19, no. 11, pp. 7289–7304, 1999. View at Google Scholar · View at Scopus
  41. L. J. Pike, “Lipid rafts: bringing order to chaos,” Journal of Lipid Research, vol. 44, no. 4, pp. 655–667, 2003. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  42. T. Fujimoto, “Calcium pump of the plasma membrane is localized in caveolae,” Journal of Cell Biology, vol. 120, no. 5, pp. 1147–1158, 1993. View at Google Scholar · View at Scopus
  43. D. P. McEwen, Q. Li, S. Jackson, P. M. Jenkins, and J. R. Martens, “Caveolin regulates Kv1.5 trafficking to cholesterol-rich membrane microdomains,” Molecular Pharmacology, vol. 73, no. 3, pp. 678–685, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  44. M. Isshiki and R. G. W. Anderson, “Function of caveolae in Ca2+ entry and Ca2+-dependent signal transduction,” Traffic, vol. 4, no. 11, pp. 717–723, 2003. View at Publisher · View at Google Scholar · View at Scopus
  45. D. Gingras, F. Gauthier, S. Lamy, R. R. Desrosiers, and R. Béliveau, “Localization of RhoA GTPase to endothelial caveolae-enriched membrane domains,” Biochemical and Biophysical Research Communications, vol. 247, no. 3, pp. 888–893, 1998. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  46. C. Dubroca, X. Loyer, K. Retailleau et al., “RhoA activation and interaction with caveolin-1 are critical for pressure-induced myogenic tone in rat mesenteric resistance arteries,” Cardiovascular Research, vol. 73, no. 1, pp. 190–197, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  47. M. J. Taggart, “Smooth muscle excitation-contraction coupling: a role for caveolae and caveolins?” News in Physiological Sciences, vol. 16, no. 2, pp. 61–65, 2001. View at Google Scholar · View at Scopus
  48. A. Adebiyi, D. Narayanan, and J. H. Jaggar, “Caveolin-1 assembles type 1 inositol 1,4,5-trisphosphate receptors and canonical transient receptor potential 3 channels into a functional signaling complex in arterial smooth muscle cells,” The Journal of Biological Chemistry, vol. 286, no. 6, pp. 4341–4348, 2011. View at Publisher · View at Google Scholar · View at PubMed
  49. T. Murata, M. I. Lin, R. V. Stan, P. M. Bauer, J. Yu, and W. C. Sessa, “Genetic evidence supporting caveolae microdomain regulation of calcium entry in endothelial cells,” The Journal of Biological Chemistry, vol. 282, no. 22, pp. 16631–16643, 2007. View at Publisher · View at Google Scholar · View at PubMed
  50. J. P. Gratton, J. Fontana, D. S. O'Connor, G. García-Cardeña, T. J. McCabe, and W. C. Sessa, “Reconstitution of an endothelial nitric-oxide synthase (eNOS), hsp90, and caveolin-1 complex in vitro: evidence that hsp90 facilitates calmodulin stimulated displacement of eNOS from caveolin-1,” The Journal of Biological Chemistry, vol. 275, no. 29, pp. 22268–22272, 2000. View at Publisher · View at Google Scholar · View at PubMed
  51. O. Feron, F. Saldana, J. B. Michel, and T. Michel, “The endothelial nitric-oxide synthase-caveolin regulatory cycle,” The Journal of Biological Chemistry, vol. 273, no. 6, pp. 3125–3128, 1998. View at Publisher · View at Google Scholar
  52. P. Sonveaux, P. Martinive, J. DeWever et al., “Caveolin-1 expression is critical for vascular endothelial growth factor-induced ischemic hindlimb collateralization and nitric oxide-mediated angiogenesis,” Circulation Research, vol. 95, no. 2, pp. 154–161, 2004. View at Publisher · View at Google Scholar · View at PubMed
  53. C. Griffoni, E. Spisni, S. Santi, M. Riccio, T. Guarnieri, and V. Tomasi, “Knockdown of caveolin-1 by antisense oligonucleotides impairs angiogenesis in vitro and in vivo,” Biochemical and Biophysical Research Communications, vol. 276, no. 2, pp. 756–761, 2000. View at Publisher · View at Google Scholar · View at PubMed
  54. J. Liu, X. B. Wang, D. S. Park, and M. P. Lisanti, “Caveolin-1 expression enhances endothelial capillary tubule formation,” The Journal of Biological Chemistry, vol. 277, no. 12, pp. 10661–10668, 2002. View at Publisher · View at Google Scholar · View at PubMed
  55. A. E. Linder, L. P. McCluskey, K. R. Cole III, K. M. Lanning, and R. C. Webb, “Dynamic association of nitric oxide downstream signaling molecules with endothelial caveolin-1 in rat aorta,” Journal of Pharmacology and Experimental Therapeutics, vol. 314, no. 1, pp. 9–15, 2005. View at Publisher · View at Google Scholar · View at PubMed
  56. J. Saliez, C. Bouzin, G. Rath et al., “Role of caveolar compartmentation in endothelium-derived hyperpolarizing factor-mediated relaxation-Ca2+ signals and gap junction function are regulated by caveolin in endothelial cells,” Circulation, vol. 117, no. 8, pp. 1065–1074, 2008. View at Publisher · View at Google Scholar · View at PubMed
  57. E. Spisni, C. Griffoni, S. Santi et al., “Colocalization prostacyclin (PGI2) synthase-caveolin-1 in endothelial cells and new roles for PGI2 in angiogenesis,” Experimental Cell Research, vol. 266, no. 1, pp. 31–43, 2001. View at Publisher · View at Google Scholar · View at PubMed
  58. L. Labrecque, I. Royal, D. S. Surprenant, C. Patterson, D. Gingras, and R. Béliveau, “Regulation of vascular endothelial growth factor receptor-2 activity by caveolin-1 and plasma membrane cholesterol,” Molecular Biology of the Cell, vol. 14, no. 1, pp. 334–347, 2003. View at Publisher · View at Google Scholar · View at PubMed
  59. J. Yu, S. Bergaya, T. Murata et al., “Direct evidence for the role of caveolin-1 and caveolae in mechanotransduction and remodeling of blood vessels,” Journal of Clinical Investigation, vol. 116, no. 5, pp. 1284–1291, 2006. View at Publisher · View at Google Scholar · View at PubMed
  60. A. D. van der Meer, M. M. Kamphuis, A. A. Poot, J. Feijen, and J. Vermes, “Lowering caveolin-1 expression in human vascular endothelial cells inhibits signal transduction in response to shear stress,” International Journal of Cell Biology, vol. 2009, Article ID 532432, 9 pages, 2009. View at Publisher · View at Google Scholar · View at PubMed
  61. F. Galbiati, D. Volonté, J. A. Engelman et al., “Targeted downregulation of caveolin-1 is sufficient to drive cell transformation and hyperactivate the p42/44 MAP kinase cascade,” The EMBO Journal, vol. 17, no. 22, pp. 6633–6648, 1998. View at Google Scholar
  62. T. M. Williams and M. P. Lisanti, “Caveolin-1 in oncogenic transformation, cancer, and metastasis,” American Journal of Physiology, vol. 288, no. 3 57-3, pp. C494–C506, 2005. View at Publisher · View at Google Scholar · View at PubMed
  63. J. A. Engelman, X. L. Zhang, B. Razani, R. G. Pestell, and M. P. Lisanti, “p42/44 MAP kinase-dependent and -independent signaling pathways regulate caveolin-1 gene expression. Activation of Ras-MAP kinase and protein kinase a signaling cascades transcriptionally down-regulates caveolin-1 promoter activity,” The Journal of Biological Chemistry, vol. 274, no. 45, pp. 32333–32341, 1999. View at Publisher · View at Google Scholar
  64. P. Gargalovic and L. Dory, “Cellular apoptosis is associated with increased caveolin-1 expression in macrophages,” Journal of Lipid Research, vol. 44, no. 9, pp. 1622–1632, 2003. View at Publisher · View at Google Scholar · View at PubMed
  65. F. Galbiati, D. Volonte', J. Liu et al., “Caveolin-1 expression negatively regulates cell cycle progression by inducing G0/G1 arrest via a p53/p21WAF1/Cip1-dependent mechanism,” Molecular Biology of the Cell, vol. 12, no. 8, pp. 2229–2244, 2001. View at Google Scholar
  66. V. A. Torres, J. C. Tapia, D. A. Rodríguez et al., “Caveolin-1 controls cell proliferation and cell death by suppressing expression of the inhibitor of apoptosis protein survivin,” Journal of Cell Science, vol. 119, no. 9, pp. 1812–1823, 2006. View at Publisher · View at Google Scholar · View at PubMed
  67. M. Yamamoto, Y. Toya, R. A. Jensen, and Y. Ishikawa, “Caveolin is an inhibitor of platelet-derived growth factor receptor signaling,” Experimental Cell Research, vol. 247, no. 2, pp. 380–388, 1999. View at Publisher · View at Google Scholar · View at PubMed
  68. T. E. Peterson, M. E. Guicciardi, R. Gulati et al., “Caveolin-1 can regulate vascular smooth muscle cell fate by switching platelet-derived growth factor signaling from a proliferative to an apoptotic pathway,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 23, no. 9, pp. 1521–1527, 2003. View at Publisher · View at Google Scholar · View at PubMed
  69. R. Zemans and G. P. Downey, “Role of caveolin-1 in regulation of inflammation: different strokes for different folks,” American Journal of Physiology, vol. 294, no. 2, pp. L175–L177, 2008. View at Publisher · View at Google Scholar · View at PubMed
  70. M. K. Mirza, J. Yuan, X. P. Gao et al., “Caveolin-1 deficiency dampens toll-like receptor 4 signaling through eNOS activation,” American Journal of Pathology, vol. 176, no. 5, pp. 2344–2351, 2010. View at Publisher · View at Google Scholar · View at PubMed
  71. Y. Jin, S.-J. Lee, R. D. Minshall, and A. M.K. Choi, “Caveolin-1: a critical regulator of lung injury,” American Journal of Physiology, vol. 300, no. 2, pp. L151–L160, 2011. View at Publisher · View at Google Scholar · View at PubMed
  72. M. Bucci, J. P. Gratton, R. D. Rudic et al., “In vivo delivery of the caveolin-1 scaffolding domain inhibits nitric oxide synthesis and reduces inflammation,” Nature Medicine, vol. 6, no. 12, pp. 1362–1367, 2000. View at Publisher · View at Google Scholar · View at PubMed
  73. G. Hu, R. D. Ye, M. C. Dinauer, A. B. Malik, and R. D. Minshall, “Neutrophil caveolin-1 expression contributes to mechanism of lung inflammation and injury,” American Journal of Physiology, vol. 294, no. 2, pp. L178–L186, 2008. View at Publisher · View at Google Scholar · View at PubMed
  74. S. F. Chen, J. Y. Liou, T. Y. Huang et al., “Caveolin-1 facilitates cyclooxygenase-2 protein degradation,” Journal of Cellular Biochemistry, vol. 109, no. 2, pp. 356–362, 2010. View at Publisher · View at Google Scholar · View at PubMed
  75. B. Razani, X. L. Zhang, M. Bitzer, G. Von Gersdorff, E. P. Böttinger, and M. P. Lisanti, “Caveolin-1 regulates transforming growth factor (TGF)-β/SMAD signaling through an interaction with the TGF-β type I receptor,” The Journal of Biological Chemistry, vol. 276, no. 9, pp. 6727–6738, 2001. View at Publisher · View at Google Scholar · View at PubMed
  76. J. F. Santibanez, F. J. Blanco, E. M. Garrido-Martin, F. Sanz-Rodriguez, M. A. Del Pozo, and C. Bernabeu, “Caveolin-1 interacts and cooperates with the transforming growth factor-β type I receptor ALK1 in endothelial caveolae,” Cardiovascular Research, vol. 77, no. 4, pp. 791–799, 2008. View at Publisher · View at Google Scholar · View at PubMed
  77. R. Mathew, “Inflammation and pulmonary hypertension,” Cardiology in Review, vol. 18, no. 2, pp. 67–72, 2010. View at Publisher · View at Google Scholar · View at PubMed
  78. M. Debidda, L. Wang, H. Zang, V. Poli, and Y. Zheng, “A role of STAT3 in Rho GTPase-regulated cell migration and proliferation,” The Journal of Biological Chemistry, vol. 280, no. 17, pp. 17275–17285, 2005. View at Publisher · View at Google Scholar · View at PubMed
  79. J. F. Jasmin, I. Mercier, F. Sotgia, and M. P. Lisanti, “SOCS proteins and caveolin-1 as negative regulators of endocrine signaling,” Trends in Endocrinology and Metabolism, vol. 17, no. 4, pp. 150–158, 2006. View at Publisher · View at Google Scholar · View at PubMed
  80. J. Huang, P. M. Kaminski, J. G. Edwards et al., “Pyrrolidine dithiocarbamate restores endothelial cell membrane integrity and attenuates monocrotaline-induced pulmonary artery hypertension,” American Journal of Physiology, vol. 294, no. 6, pp. L1250–L1259, 2008. View at Publisher · View at Google Scholar · View at PubMed
  81. J. F. Jasmin, I. Mercier, J. Dupuis, H. B. Tanowitz, and M. P. Lisanti, “Short-term administration of a cell-permeable caveolin-1 peptide prevents the development of monocrotaline-induced pulmonary hypertension and right ventricular hypertrophy,” Circulation, vol. 114, no. 9, pp. 912–920, 2006. View at Publisher · View at Google Scholar · View at PubMed
  82. R. Mathew, J. Huang, and M. H. Gewitz, “Pulmonary artery hypertension: caveolin-1 and eNOS interrelationship: a new perspective,” Cardiology in Review, vol. 15, no. 3, pp. 143–149, 2007. View at Publisher · View at Google Scholar · View at PubMed
  83. B. Razani, X. B. Wang, J. A. Engelman et al., “Caveolin-2-deficient mice show evidence of severe pulmonary dysfunction without disruption of caveolae,” Molecular and Cellular Biology, vol. 22, no. 7, pp. 2329–2344, 2002. View at Publisher · View at Google Scholar
  84. J. A. Barberà, V. I. Peinado, and S. Santos, “Pulmonary hypertension in chronic obstructive pulmonary disease,” European Respiratory Journal, vol. 21, no. 5, pp. 892–905, 2003. View at Publisher · View at Google Scholar
  85. T. Murata, K. Sato, M. Hori, H. Ozaki, and H. Karaki, “Decreased endothelial nitric-oxide synthase (eNOS) activity resulting from abnormal interaction between eNOS and its regulatory proteins in hypoxia-induced pulmonary hypertension,” The Journal of Biological Chemistry, vol. 277, no. 46, pp. 44085–44092, 2002. View at Publisher · View at Google Scholar · View at PubMed
  86. S. Adnot, B. Raffestin, S. Eddahibi, P. Braquet, and P. E. Chabrier, “Loss of endothelium-dependent relaxant activity in the pulmonary circulation of rats exposed to chronic hypoxia,” Journal of Clinical Investigation, vol. 87, no. 1, pp. 155–162, 1991. View at Google Scholar
  87. R. Mathew, N. Yuan, L. Rosenfeld, M. H. Gewitz, and A. Kumar, “Effects of monocrotaline on endothelial nitric oxide synthase expression and sulfhydryl levels in rat lungs,” Heart Disease, vol. 4, no. 3, pp. 152–158, 2002. View at Google Scholar
  88. J. Liu, Y. Gao, S. Negash, L. D. Longo, and J. U. Raj, “Long-term effects of prenatal hypoxia on endothelium-dependent relaxation responses in pulmonary arteries of adult sheep,” American Journal of Physiology, vol. 296, no. 3, pp. L547–L554, 2009. View at Publisher · View at Google Scholar · View at PubMed
  89. R. Mathew, J. Huang, X. Zhao et al., “Activation of signal transducer and transcription of (STAT) 3 in hypoxia-induced pulmonary hypertension,” The FASEB Journal, vol. 21, p. A1435, abstract, 2007. View at Google Scholar
  90. K. Schultz, B. L. Fanburg, and D. Beasley, “Hypoxia and hypoxia-inducible factor-1α promote growth factor-induced proliferation of human vascular smooth muscle cells,” American Journal of Physiology, vol. 290, no. 6, pp. H2528–H2534, 2006. View at Publisher · View at Google Scholar · View at PubMed
  91. J. E. Jung, H. G. Lee, IK. H. Cho et al., “STAT3 is a potential modulator of HIF-1-mediated VEGF expression in human renal carcinoma cells,” The FASEB Journal, vol. 19, no. 10, pp. 1296–1298, 2005. View at Publisher · View at Google Scholar · View at PubMed
  92. Q. Xu, J. Briggs, S. Park et al., “Targeting Stat3 blocks both HIF-1 and VEGF expression induced by multiple oncogenic growth signaling pathways,” Oncogene, vol. 24, no. 36, pp. 5552–5560, 2005. View at Publisher · View at Google Scholar · View at PubMed
  93. T. Murata, K. Kinoshita, M. Hori et al., “Statin protects endothelial nitric oxide synthase activity in hypoxia-induced pulmonary hypertension,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 25, no. 11, pp. 2335–2342, 2005. View at Publisher · View at Google Scholar · View at PubMed
  94. B. M. Ewenstein, M. J. Warhol, R. I. Handin, and J. S. Pober, “Composition of the von Willebrand factor storage organelle (Weibel-Palade body) isolated from cultured human umbilical vein endothelial cells,” Journal of Cell Biology, vol. 104, no. 5, pp. 1423–1433, 1987. View at Google Scholar
  95. S. M. Kawut, E. M. Horn, K. K. Berekashvili, A. C. Widlitz, E. B. Rosenzweig, and R. J. Barst, “von Willebrand factor independently predicts long-term survival in patients with pulmonary arterial hypertension,” Chest, vol. 128, no. 4, pp. 2355–2362, 2005. View at Publisher · View at Google Scholar · View at PubMed
  96. S. Sakao, L. Taraseviciene-Stewart, J. D. Lee, K. Wood, C. D. Cool, and N. F. Voelkel, “Initial apoptosis is followed by increased proliferation of apoptosis-resistant endothelial cells,” The FASEB Journal, vol. 19, no. 9, pp. 1178–1180, 2005. View at Publisher · View at Google Scholar · View at PubMed
  97. G. Gabella and D. Blundell, “Effect of stretch and contraction on caveolae of smooth muscle cells,” Cell and Tissue Research, vol. 190, no. 2, pp. 255–271, 1978. View at Google Scholar
  98. L. C. Huber, A. Soltermann, M. Fischler et al., “Caveolin-1 expression and hemodynamics in COPD patients,” Open Respiratory Medicine Journal, vol. 3, pp. 73–78, 2009. View at Publisher · View at Google Scholar · View at PubMed
  99. J. Thyberg, “Caveolin-1 and caveolae act as regulators of mitogenic signaling in vascular smooth muscle cells,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 23, no. 9, pp. 1481–1483, 2003. View at Publisher · View at Google Scholar · View at PubMed
  100. J.-I. Kawabe, S. Okumura, M.-C. Lee, J. Sadoshima, and Y. Ishikawa, “Translocation of caveolin regulates stretch-induced ERK activity in vascular smooth muscle cells,” American Journal of Physiology, vol. 286, no. 5, pp. H1845–H1852, 2004. View at Publisher · View at Google Scholar · View at PubMed
  101. D. G. Sedding and R. C. Braun-Dullaeus, “Caveolin-1: dual role for proliferation of vascular smooth muscle cells,” Trends in Cardiovascular Medicine, vol. 16, no. 2, pp. 50–55, 2006. View at Publisher · View at Google Scholar · View at PubMed
  102. M. M. Hill, M. Bastiani, R. Luetterforst et al., “PTRF-cavin, a conserved cytoplasmic protein required for caveola formation and function,” Cell, vol. 132, no. 1, pp. 113–124, 2008. View at Publisher · View at Google Scholar · View at PubMed
  103. B. Sinha, D. Köster, R. Ruez et al., “Cells respond to mechanical stress by rapid disassembly of caveolae,” Cell, vol. 144, no. 3, pp. 402–413, 2011. View at Publisher · View at Google Scholar · View at PubMed
  104. B. Annabi, M. Lachambre, N. P. Bousquet-Gagnon, M. Pagé, D. Gingras, and R. Béliveau, “Localization of membrane-type 1 matrix metalloproteinase in caveolae membrane domains,” Biochemical Journal, vol. 353, no. 3, pp. 547–553, 2001. View at Publisher · View at Google Scholar
  105. A. C. Newby, “Matrix metalloproteinases regulate migration, proliferation, and death of vascular smooth muscle cells by degrading matrix and non-matrix substrates,” Cardiovascular Research, vol. 69, no. 3, pp. 614–624, 2006. View at Publisher · View at Google Scholar · View at PubMed
  106. R. R. Pauly, A. Passaniti, C. Bilato et al., “Migration of cultured vascular smooth muscle cells through a basement membrane barrier requires type IV collagenase activity and is inhibited by cellular differentiation,” Circulation Research, vol. 75, no. 1, pp. 41–54, 1994. View at Google Scholar
  107. T. M. Williams, F. Medina, I. Badano et al., “Caveolin-1 gene disruption promotes mammary tumorigenesis and dramatically enhances lung metastasis in vivo: role of Cav-1 in cell invasiveness and matrix metalloproteinase (MMP-2/9) secretion,” The Journal of Biological Chemistry, vol. 279, no. 49, pp. 51630–51646, 2004. View at Publisher · View at Google Scholar · View at PubMed
  108. J. W. Wertz and P. M. Bauer, “Caveolin-1 regulates BMPRII localization and signaling in vascular smooth muscle cells,” Biochemical and Biophysical Research Communications, vol. 375, no. 4, pp. 557–561, 2008. View at Publisher · View at Google Scholar · View at PubMed
  109. M. Beiderlinden, H. Kuehl, T. Boes, and J. Peters, “Prevalence of pulmonary hypertension associated with severe acute respiratory distress syndrome: predictive value of computed tomography,” Intensive Care Medicine, vol. 32, no. 6, pp. 852–857, 2006. View at Publisher · View at Google Scholar · View at PubMed
  110. S. Saharan, R. Lodha, and S. K. Kabra, “Management of acute lung injury/ARDS,” Indian Journal of Pediatrics, vol. 77, no. 11, pp. 1296–1302, 2010. View at Publisher · View at Google Scholar · View at PubMed
  111. M. A. Matthay and R. L. Zemans, “The acute respiratory distress syndrome: pathogenesis and treatment,” Annual Review of Pathology, vol. 6, pp. 147–163, 2011. View at Publisher · View at Google Scholar · View at PubMed
  112. L. B. Ware, E. R. Conner, and M. A. Matthay, “von Willebrand factor antigen is an independent marker of poor outcome in patients with early acute lung injury,” Critical Care Medicine, vol. 29, no. 12, pp. 2325–2331, 2001. View at Google Scholar
  113. R. Gosens, G. L. Stelmack, St. Bos et al., “Caveolin-1 is required for contractile phenotype expression by airway smooth muscle cells,” Journal of Cellular and Molecular Medicine. In press. View at Publisher · View at Google Scholar · View at PubMed
  114. R. Gosens, G. L. Stelmack, G. Dueck et al., “Role of caveolin-1 in p42/p44 MAP kinase activation and proliferation of human airway smooth muscle,” American Journal of Physiology, vol. 291, no. 3, pp. L523–L534, 2006. View at Publisher · View at Google Scholar · View at PubMed
  115. G. S. Hassan, T. M. Williams, P. G. Frank, and M. P. Lisanti, “Caveolin-1-deficient aortic smooth muscle cells show cell autonomous abnormalities in proliferation, migration, and endothelin-based signal transduction,” American Journal of Physiology, vol. 290, no. 6, pp. H2393–H2401, 2006. View at Publisher · View at Google Scholar · View at PubMed
  116. B. Razani, J. A. Engelman, X. B. Wang et al., “Caveolin-1 null mice are viable but show evidence of hyperproliferative and vascular abnormalities,” The Journal of Biological Chemistry, vol. 276, no. 41, pp. 38121–38138, 2001. View at Google Scholar
  117. D. S. Park, A. W. Cohen, P. G. Frank et al., “Caveolin-1 null (-/-) mice show dramatic reductions in life span,” Biochemistry, vol. 42, no. 51, pp. 15124–15131, 2003. View at Publisher · View at Google Scholar · View at PubMed
  118. M. Drab, P. Verkade, M. Elger et al., “Loss of caveolae, vascular dysfunction, and pulmonary defects in caveolin-1 gene-disrupted mice,” Science, vol. 293, no. 5539, pp. 2449–2452, 2001. View at Publisher · View at Google Scholar · View at PubMed
  119. Y. Y. Zhao, Y. Liu, R. V. Stan et al., “Defects in caveolin-1 cause dilated cardiomyopathy and pulmonary hypertension in knockout mice,” Proceedings of the National Academy of Sciences of the United States of America, vol. 99, no. 17, pp. 11375–11380, 2002. View at Publisher · View at Google Scholar · View at PubMed
  120. J. Liu, P. Lee, F. Galbiati, R. N. Kitsis, and M. P. Lisanti, “Caveolin-1 expression sensitizes fibroblastic and epithelial cells to apoptotic stimulation,” American Journal of Physiology, vol. 280, no. 4, pp. C823–C835, 2001. View at Google Scholar
  121. T. Murata, M. I. Lin, Y. Huang et al., “Reexpression of caveolin-1 in endothelium rescues the vascular, cardiac, and pulmonary defects in global caveolin-1 knockout mice,” Journal of Experimental Medicine, vol. 204, no. 10, pp. 2373–2382, 2007. View at Publisher · View at Google Scholar · View at PubMed
  122. R. C. Tyler, M. Muramatsu, S. H. Abman et al., “Variable expression of endothelial no synthase in three forms of rat pulmonary hypertension,” American Journal of Physiology, vol. 276, no. 2, pp. L297–L303, 1999. View at Google Scholar
  123. Y.-Y. Zhao, Y. D. Zhao, M. K. Mirza et al., “Persistent eNOS activation secondary to caveolin-1 deficiency induces pulmonary hypertension in mice and humans through PKG nitration,” Journal of Clinical Investigation, vol. 119, no. 7, pp. 2009–2018, 2009. View at Publisher · View at Google Scholar · View at PubMed
  124. N. A. Mason, D. R. Springall, M. Burke et al., “High expression of endothelial nitric oxide synthase in plexiform lesions of pulmonary hypertension,” Journal of Pathology, vol. 185, no. 3, pp. 313–318, 1998. View at Publisher · View at Google Scholar
  125. A. Giaid and D. Saleh, “Reduced expression of endothelial nitric oxide synthase in the lungs of patients with pulmonary hypertension,” The New England Journal of Medicine, vol. 333, no. 4, pp. 214–221, 1995. View at Publisher · View at Google Scholar · View at PubMed
  126. R. K. Gupta and P. Vaideeswar, “Nitric oxide synthase 3 and endothelin 1 immunoreactivity in pulmonary hypertension,” Indian Journal of Pathology & Microbiology, vol. 53, no. 3, pp. 447–450, 2010. View at Google Scholar
  127. B. S. Zuckerbraun, P. George, and M. T. Gladwin, “Nitrite in pulmonary arterial hypertension: therapeutic avenues in the setting of dysregulated arginine/nitric oxide synthase signalling,” Cardiovascular Research, vol. 89, no. 3, pp. 542–552, 2011. View at Publisher · View at Google Scholar · View at PubMed
  128. R. Mathew, N. Y. T. Fan, N. Yuan, P. N. Chander, M. H. Gewitz, and C. T. Stier, “Inhibition of NOS enhances pulmonary vascular changes in stroke-prone spontaneously hypertensive rats,” American Journal of Physiology, vol. 278, no. 1, pp. L81–L89, 2000. View at Google Scholar
  129. E. Burgermeister, M. Liscovitch, C. Röcken, R. M. Schmid, and M. P. A. Ebert, “Caveats of caveolin-1 in cancer progression,” Cancer Letters, vol. 268, no. 2, pp. 187–201, 2008. View at Publisher · View at Google Scholar · View at PubMed
  130. A. F. G. Quest, J. L. Gutierrez-Pajares, and V. A. Torres, “Caveolin-1: an ambiguous partner in cell signalling and cancer,” Journal of Cellular and Molecular Medicine, vol. 12, no. 4, pp. 1130–1150, 2008. View at Publisher · View at Google Scholar · View at PubMed
  131. C. Trimmer, D. Whitaker-Menezes, G. Bonuccelli et al., “CAV1 inhibits metastatic potential in melanomas through suppression of the integrin/Src/FAK signaling pathway,” Cancer Research, vol. 70, no. 19, pp. 7489–7499, 2010. View at Publisher · View at Google Scholar · View at PubMed