Reduced BMPR2 expression induces GM-CSF translation and macrophage recruitment in humans and mice to exacerbate pulmonary hypertension

Journal of Experimental Medicine

Volumn 211, Issue 2, 2014, Pages 263-280

  Sawada, Hirofumi ^a   Saito, Toshie ^a   Nickel, Nils P ^a   Alastalo, Tero Pekka ^a   Glotzbach, Jason P ^a   Chan, Roshelle ^a   Haghighat, Leila ^a   Fuchs, Gabriele ^a   Januszyk, Michael ^a   Cao, Aiqin ^a   Lai, Ying Ju ^a   de Jesus Perez, Vinicio ^a   Kim, Yu Mee ^a   Wang, Lingli ^a   Chen, Pin I ^a   Spiekerkoetter, Edda ^a   Mitani, Yoshihide ^b   Gurtner, Geoffrey C ^a   Sarnow, Peter ^a   Rabinovitch, Marlene ^a  

^a STANFORD UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b MIE UNIVERSITY GRADUATE SCHOOL OF MEDICINE   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

ADOLESCENT; ADULT; ANIMALS; BONE MORPHOGENETIC PROTEIN RECEPTORS, TYPE II; CASE-CONTROL STUDIES; CHILD; ENDOTHELIAL CELLS; EUKARYOTIC INITIATION FACTOR-2; FEMALE; GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR; HUMANS; HYPERTENSION, PULMONARY; MACROPHAGES; MALE; MAP KINASE SIGNALING SYSTEM; MICE; MICE, INBRED C57BL; MIDDLE AGED; MYOCYTES, SMOOTH MUSCLE; PROTEIN BIOSYNTHESIS; PROTEIN PHOSPHATASE 1; PULMONARY ARTERY; RATS; RATS, SPRAGUE-DAWLEY; RECEPTORS, GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR; RNA, MESSENGER; RNA, SMALL INTERFERING; YOUNG ADULT;

EID: 84893783838     PISSN: 00221007     EISSN: 15409538     Source Type: Journal    
DOI: 10.1084/jem.20111741     Document Type: Article

References (72)

1. Alastalo, T.P., M. Li, V.J. Perez, D. Pham, H. Sawada, J.K. Wang, M. Koskenvuo, L. Wang, B.A. Freeman, H.Y. Chang, and M. Rabinovitch. 2011. Disruption of PPARα/α-catenin-mediated regulation of apelin impairs BMP-induced mouse and human pulmonary arterial EC survival. J. Clin. Invest. 121:3735-3746. http://dx.doi.org/10.1172/JCI43382
2. Anderson, P., and N. Kedersha. 2008. Stress granules: the Tao of RNA triage. Trends Biochem. Sci. 33:141-150. http://dx.doi.org/10.1016/j.tibs.2007.12.003
3. Anderson, P., and N. Kedersha. 2009. RNA granules: post-transcriptional and epigenetic modulators of gene expression. Nat. Rev. Mol. Cell Biol. 10:430-436. http://dx.doi.org/10.1038/nrm2694
4. Asosingh, K., M.A. Aldred, A. Vasanji, J. Drazba, J. Sharp, C. Farver, S.A. Comhair, W. Xu, L. Licina, L. Huang, et al. 2008. Circulating angiogenic precursors in idiopathic pulmonary arterial hypertension. Am. J. Pathol. 172:615-627. http://dx.doi.org/10.2353/ajpath.2008.070705
5. Atkinson, C., S. Stewart, P.D. Upton, R. Machado, J.R. Thomson, R.C. Trembath, and N.W. Morrell. 2002. Primary pulmonary hypertension is associated with reduced pulmonary vascular expression of type II bone morphogenetic protein receptor. Circulation. 105:1672-1678. http://dx.doi.org/10.1161/01.CIR.0000012754.72951.3D
6. Boyce, M., K.F. Bryant, C. Jousse, K. Long, H.P. Harding, D. Scheuner, R.J. Kaufman, D. Ma, D.M. Coen, D. Ron, and J. Yuan. 2005. A selective inhibitor of eIF2alpha dephosphorylation protects cells from ER stress. Science. 307:935-939. http://dx.doi.org/10.1126/science.1101902
7. Brissette, W.H., D.A. Baker, E.J. Stam, J.P. Umland, and R.J. Griffiths. 1995. GM-CSF rapidly primes mice for enhanced cytokine production in response to LPS and TNF. Cytokine. 7:291-295. http://dx.doi.org/10.1006/cyto.1995.0035
8. Brown, J.A., T.L. Roberts, R. Richards, R. Woods, G. Birrell, Y.C. Lim, S. Ohno, A. Yamashita, R.T. Abraham, N. Gueven, and M.F. Lavin. 2011. A novel role for hSMG-1 in stress granule formation. Mol. Cell. Biol. 31:4417-4429. http://dx.doi.org/10.1128/MCB.05987-11
9. Brush, M.H., D.C. Weiser, and S. Shenolikar. 2003. Growth arrest and DNA damage-inducible protein GADD34 targets protein phosphatase 1 alpha to the endoplasmic reticulum and promotes dephosphorylation of the alpha subunit of eukaryotic translation initiation factor 2. Mol. Cell. Biol. 23:1292-1303. http://dx.doi.org/10.1128/MCB.23.4.1292-1303.2003
10. Burgess, A.W., and D. Metcalf. 1980. The nature and action of granulocytemacrophage colony stimulating factors. Blood. 56:947-958.
11. Bussolino, F., J.M. Wang, P. Defilippi, F. Turrini, F. Sanavio, C.J. Edgell, M. Aglietta, P. Arese, and A. Mantovani. 1989. Granulocyte-and granulocyte-macrophage-colony stimulating factors induce human endothelial cells to migrate and proliferate. Nature. 337:471-473. http://dx.doi.org/10.1038/337471a0
12. Cool, C.D., P.R. Rai, M.E. Yeager, D. Hernandez-Saavedra, A.E. Serls, T.M. Bull, M.W. Geraci, K.K. Brown, J.M. Routes, R.M. Tuder, and N.F. Voelkel. 2003. Expression of human herpesvirus 8 in primary pulmonary hypertension. N. Engl. J. Med. 349:1113-1122. http://dx.doi.org/10.1056/NEJMoa035115
13. Crane, I.J., M.C. Kuppner, S. McKillop-Smith, C.A. Wallace, and J.V. Forrester. 1999. Cytokine regulation of granulocyte-macrophage colony-stimulating factor (GM-CSF) production by human retinal pigment epithelial cells. Clin. Exp. Immunol. 115:288-293.
14. Davie, N.J., J.T. Crossno Jr., M.G. Frid, S.E. Hofmeister, J.T. Reeves, D.M. Hyde, T.C. Carpenter, J.A. Brunetti, I.K. McNiece, and K.R. Stenmark. 2004. Hypoxia-induced pulmonary artery adventitial remodeling and neovascularization: contribution of progenitor cells. Am. J. Physiol. Lung Cell. Mol. Physiol. 286:L668-L678. http://dx.doi.org/10.1152/ajplung.00108.2003
15. Detmar, M., S. Tenorio, U. Hettmannsperger, Z. Ruszczak, and C.E. Orfanos. 1992. Cytokine regulation of proliferation and ICAM-1 expression of human dermal microvascular endothelial cells in vitro. J. Invest. Dermatol. 98:147-153. http://dx.doi.org/10.1111/1523-1747.ep12555746
16. Diehn, M., R.W. Cho, N.A. Lobo, T. Kalisky, M.J. Dorie, A.N. Kulp, D. Qian, J.S. Lam, L.E. Ailles, M. Wong, et al. 2009. Association of reactive oxygen species levels and radioresistance in cancer stem cells. Nature. 458:780-783. http://dx.doi.org/10.1038/nature07733
17. Fleetwood, A.J., T. Lawrence, J.A. Hamilton, and A.D. Cook. 2007. Granulocyte-macrophage colony-stimulating factor (CSF) and macrophage CSF-dependent macrophage phenotypes display differences in cytokine profiles and transcription factor activities: implications for CSF blockade in inflammation. J. Immunol. 178:5245-5252.
18. Frid, M.G., J.A. Brunetti, D.L. Burke, T.C. Carpenter, N.J. Davie, J.T. Reeves, M.T. Roedersheimer, N. van Rooijen, and K.R. Stenmark. 2006. Hypoxia-induced pulmonary vascular remodeling requires recruitment of circulating mesenchymal precursors of a monocyte/macrophage lineage. Am. J. Pathol. 168:659-669. http://dx.doi.org/10.2353/ajpath.2006.050599
19. Fujita, M., R.J. Mason, C. Cool, J.M. Shannon, N. Hara, and K.A. Fagan. 2002. Pulmonary hypertension in TNF-alpha-overexpressing mice is associated with decreased VEGF gene expression. J. Appl. Physiol. 93:2162-2170.
20. Glotzbach, J.P., M. Januszyk, I.N. Vial, V.W. Wong, A. Gelbard, T. Kalisky, H. Thangarajah, M.T. Longaker, S.R. Quake, G. Chu, and G.C. Gurtner. 2011. An information theoretic, microfluidic-based single cell analysis permits identification of subpopulations among putatively homogeneous stem cells. PLoS ONE. 6:e21211. http://dx.doi.org/10.1371/journal.pone.0021211
21. Guignabert, C., C.M. Alvira, T.P. Alastalo, H. Sawada, G. Hansmann, M. Zhao, L. Wang, N. El-Bizri, and M. Rabinovitch. 2009. 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. 297:L1082-L1090. http://dx.doi.org/10.1152/ajplung.00199.2009
22. Hagen, M., K. Fagan, W. Steudel, M. Carr, K. Lane, D.M. Rodman, and J. West. 2007. Interaction of interleukin-6 and the BMP pathway in pulmonary smooth muscle. Am. J. Physiol. Lung Cell. Mol. Physiol. 292:L1473-L1479. http://dx.doi.org/10.1152/ajplung.00197.2006
23. Haghighat, A., D. Weiss, M.K. Whalin, D.P. Cowan, and W.R. Taylor. 2007. Granulocyte colony-stimulating factor and granulocyte macrophage colony-stimulating factor exacerbate atherosclerosis in apolipoprotein E-deficient mice. Circulation. 115:2049-2054. http://dx.doi.org/10.1161/CIRCULATIONAHA.106.665570
24. Hamilton, J.A. 2008. Colony-stimulating factors in inflammation and autoimmunity. Nat. Rev. Immunol. 8:533-544. http://dx.doi.org/10.1038/nri2356
25. Hansmann, G., V.A. de Jesus Perez, T.P. Alastalo, C.M. Alvira, C. Guignabert, J.M. Bekker, S. Schellong, T. Urashima, L. Wang, N.W. Morrell, and M. Rabinovitch. 2008. An antiproliferative BMP-2/ PPARgamma/apoE axis in human and murine SMCs and its role in pulmonary hypertension. J. Clin. Invest. 118:1846-1857. http://dx.doi.org/10.1172/JCI32503
26. Hitti, E., T. Iakovleva, M. Brook, S. Deppenmeier, A.D. Gruber, D. Radzioch, A.R. Clark, P.J. Blackshear, A. Kotlyarov, and M. Gaestel. 2006. Mitogen-activated protein kinase-activated protein kinase 2 regulates tumor necrosis factor mRNA stability and translation mainly by altering tristetraprolin expression, stability, and binding to adenine/ uridine-rich element. Mol. Cell. Biol. 26:2399-2407. http://dx.doi.org/10.1128/MCB.26.6.2399-2407.2006
27. Hong, K.H., Y.J. Lee, E. Lee, S.O. Park, C. Han, H. Beppu, E. Li, M.K. Raizada, K.D. Bloch, and S.P. Oh. 2008. Genetic ablation of the BMPR2 gene in pulmonary endothelium is sufficient to predispose to pulmonary arterial hypertension. Circulation. 118:722-730. http://dx.doi.org/10.1161/CIRCULATIONAHA.107.736801
28. Hu, S., E.C. Claud, M.W. Musch, and E.B. Chang. 2010. Stress granule formation mediates the inhibition of colonic Hsp70 translation by interferon-gamma and tumor necrosis factor-alpha. Am. J. Physiol. Gastrointest. Liver Physiol. 298:G481-G492. http://dx.doi.org/10.1152/ajpgi.00234.2009
29. Humbert, M., G. Monti, F. Brenot, O. Sitbon, A. Portier, L. Grangeot-Keros, P. Duroux, P. Galanaud, G. Simonneau, and D. Emilie. 1995. Increased interleukin-1 and interleukin-6 serum concentrations in severe primary pulmonary hypertension. Am. J. Respir. Crit. Care Med. 151:1628-1631. http://dx.doi.org/10.1164/ajrccm.151.5.7735624
30. Itoh, T., N. Nagaya, H. Ishibashi-Ueda, S. Kyotani, H. Oya, F. Sakamaki, H. Kimura, and N. Nakanishi. 2006. Increased plasma monocyte chemoattractant protein-1 level in idiopathic pulmonary arterial hypertension. Respirology. 11:158-163. http://dx.doi.org/10.1111/j.1440-1843.2006.00821.x
31. Jones, R. 1992. Ultrastructural analysis of contractile cell development in lung microvessels in hyperoxic pulmonary hypertension. Fibroblasts and intermediate cells selectively reorganize nonmuscular segments. Am. J. Pathol. 141:1491-1505.
32. Kedersha, N., and P. Anderson. 2007. Mammalian stress granules and processing bodies. Methods Enzymol. 431:61-81.
33. Keyse, S.M. 2000. Protein phosphatases and the regulation of mitogenactivated protein kinase signalling. Curr. Opin. Cell Biol. 12:186-192. http://dx.doi.org/10.1016/S0955-0674(99)00075-7
34. Kotlyarov, A., A. Neininger, C. Schubert, R. Eckert, C. Birchmeier, H.D. Volk, and M. Gaestel. 1999. MAPKAP kinase 2 is essential for LPSinduced TNF-alpha biosynthesis. Nat. Cell Biol. 1:94-97. http://dx.doi.org/10.1038/10061
35. Lane, K.B., R.D. Machado, M.W. Pauciulo, J.R. Thomson, J.A. Phillips III, J.E. Loyd, W.C. Nichols, and R.C. Trembath; International PPH Consortium. 2000. Heterozygous germline mutations in BMPR2, encoding a TGF-beta receptor, cause familial primary pulmonary hypertension. Nat. Genet. 26:81-84. http://dx.doi.org/10.1038/79226
36. Li, M., S.R. Riddle, M.G. Frid, K.C. El Kasmi, T.A. McKinsey, R.J. Sokol, D. Strassheim, B. Meyrick, M.E. Yeager, A.R. Flockton, et al. 2011. Emergence of fibroblasts with a proinflammatory epigenetically altered phenotype in severe hypoxic pulmonary hypertension. J. Immunol. 187:2711-2722. http://dx.doi.org/10.4049/jimmunol.1100479
37. Long, L., M.R. MacLean, T.K. Jeffery, I. Morecroft, X. Yang, N. Rudarakanchana, M. Southwood, V. James, R.C. Trembath, and N.W. Morrell. 2006. Serotonin increases susceptibility to pulmonary hypertension in BMPR2-deficient mice. Circ. Res. 98:818-827. http://dx.doi.org/10.1161/01.RES.0000215809.47923.fd
38. Marecki, J.C., C.D. Cool, J.E. Parr, V.E. Beckey, P.A. Luciw, A.F. Tarantal, A. Carville, R.P. Shannon, A. Cota-Gomez, R.M. Tuder, et al. 2006. HIV-1 Nef is associated with complex pulmonary vascular lesions in SHIV-nef-infected macaques. Am. J. Respir. Crit. Care Med. 174:437-445. http://dx.doi.org/10.1164/rccm.200601-005OC
39. Newman, J.H., R.C. Trembath, J.A. Morse, E. Grunig, J.E. Loyd, S. Adnot, F. Coccolo, C. Ventura, J.A. Phillips III, J.A. Knowles, et al. 2004. Genetic basis of pulmonary arterial hypertension: current understanding and future directions. J. Am. Coll. Cardiol. 43:S33-S39. http://dx.doi .org/10.1016/j.jacc.2004.02.028
40. Oh-Hashi, K., W. Maruyama, and K. Isobe. 2001. Peroxynitrite induces GADD34, 45, and 153 VIA p38 MAPK in human neuroblastoma SH-SY5Y cells. Free Radic. Biol. Med. 30:213-221. http://dx.doi.org/10.1016/S0891-5849(00)00461-5
41. Perros, F., P. Dorfmüller, D. Montani, H. Hammad, W. Waelput, B. Girerd, N. Raymond, O. Mercier, S. Mussot, S. Cohen-Kaminsky, et al. 2012. Pulmonary lymphoid neogenesis in idiopathic pulmonary arterial hypertension. Am. J. Respir. Crit. Care Med. 185:311-321. http://dx.doi.org/10.1164/rccm.201105-0927OC
42. Pietra, G.G., W.D. Edwards, J.M. Kay, S. Rich, J. Kernis, B. Schloo, S.M. Ayres, E.H. Bergofsky, B.H. Brundage, K.M. Detre, et al. 1989. Histopathology of primary pulmonary hypertension. A qualitative and quantitative study of pulmonary blood vessels from 58 patients in the National Heart, Lung, and Blood Institute, Primary Pulmonary Hypertension Registry. Circulation. 80:1198-1206. http://dx.doi.org/10.1161/01.CIR.80.5.1198
43. Rolfe, B.E., J.H. Campbell, N.J. Smith, M.W. Cheong, and G.R. Campbell. 1995. T lymphocytes affect smooth muscle cell phenotype and proliferation. Arterioscler. Thromb. Vasc. Biol. 15:1204-1210. http://dx.doi.org/10.1161/01.ATV.15.8.1204
44. Rosborough, B.R., A. Castellaneta, S. Natarajan, A.W. Thomson, and H.R. Turnquist. 2012. Histone deacetylase inhibition facilitates GMCSF-mediated expansion of myeloid-derived suppressor cells in vitro and in vivo. J. Leukoc. Biol. 91:701-709.
45. Rosenberg, H.C., and M. Rabinovitch. 1988. Endothelial injury and vascular reactivity in monocrotaline pulmonary hypertension. Am. J. Physiol. 255:H1484-H1491.
46. Rubbia-Brandt, L., A.P. Sappino, and G. Gabbiani. 1991. Locally applied GM-CSF induces the accumulation of alpha-smooth muscle actin containing myofibroblasts. Virchows Arch. B Cell Pathol. Incl. Mol. Pathol. 60:73-82. http://dx.doi.org/10.1007/BF02899530
47. Sampath, P., D.K. Pritchard, L. Pabon, H. Reinecke, S.M. Schwartz, D.R. Morris, and C.E. Murry. 2008. A hierarchical network controls protein translation during murine embryonic stem cell self-renewal and differentiation. Cell Stem Cell. 2:448-460. http://dx.doi.org/10.1016/j.stem.2008.03.013
48. Serezani, C.H., S. Kane, L. Collins, M. Morato-Marques, J.J. Osterholzer, and M. Peters-Golden. 2012. Macrophage dectin-1 expression is controlled by leukotriene B4 via a GM-CSF/PU.1 axis. J. Immunol. 189:906-915. http://dx.doi.org/10.4049/jimmunol.1200257
49. Soldi, R., L. Primo, M.F. Brizzi, F. Sanavio, M. Aglietta, N. Polentarutti, L. Pegoraro, A. Mantovani, and F. Bussolino. 1997. Activation of JAK2 in human vascular endothelial cells by granulocyte-macrophage colonystimulating factor. Blood. 89:863-872.
50. Song, Y., J.E. Jones, H. Beppu, J.F. Keaney Jr., J. Loscalzo, and Y.Y. Zhang. 2005. Increased susceptibility to pulmonary hypertension in heterozygous BMPR2-mutant mice. Circulation. 112:553-562. http://dx.doi.org/10.1161/CIRCULATIONAHA.104.492488
51. Soon, E., A.M. Holmes, C.M. Treacy, N.J. Doughty, L. Southgate, R.D. Machado, R.C. Trembath, S. Jennings, L. Barker, P. Nicklin, et al. 2010. Elevated levels of inflammatory cytokines predict survival in idiopathic and familial pulmonary arterial hypertension. Circulation. 122:920-927. http://dx.doi.org/10.1161/CIRCULATIONAHA.109.933762
52. Speich, R., R. Jenni, M. Opravil, M. Pfab, and E.W. Russi. 1991. Primary pulmonary hypertension in HIV infection. Chest. 100:1268-1271. http://dx.doi.org/10.1378/chest.100.5.1268
53. Spiekerkoetter, E., C.M. Alvira, Y.M. Kim, A. Bruneau, K.L. Pricola, L. Wang, N. Ambartsumian, and M. Rabinovitch. 2008. Reactivation of gammaHV68 induces neointimal lesions in pulmonary arteries of S100A4/Mts1-overexpressing mice in association with degradation of elastin. Am. J. Physiol. Lung Cell. Mol. Physiol. 294:L276-L289. http://dx.doi.org/10.1152/ajplung.00414.2007
54. Steiner, M.K., O.L. Syrkina, N. Kolliputi, E.J. Mark, C.A. Hales, and A.B. Waxman. 2009. Interleukin-6 overexpression induces pulmonary hypertension.Circ. Res. 104:236-244. http://dx.doi.org/10.1161/CIRCRESAHA.108.182014
55. Stenmark, K.R., N.J. Davie, J.T. Reeves, and M.G. Frid. 2005. Hypoxia, leukocytes, and the pulmonary circulation. J. Appl. Physiol. 98:715-721. http://dx.doi.org/10.1152/japplphysiol.00840.2004
56. Stevens, T., P.L. Janssen, and A.D. Tucker. 1992. Acute and long-term TNF-alpha administration increases pulmonary vascular reactivity in isolated rat lungs. J. Appl. Physiol. 73:708-712.
57. Takahashi, T., C. Kalka, H. Masuda, D. Chen, M. Silver, M. Kearney, M. Magner, J.M. Isner, and T. Asahara. 1999. Ischemia-and cytokine-induced mobilization of bone marrow-derived endothelial progenitor cells for neovascularization. Nat. Med. 5:434-438. http://dx.doi.org/10.1038/7434
58. Tamosiuniene, R., W. Tian, G. Dhillon, L. Wang, Y.K. Sung, L. Gera, A.J. Patterson, R. Agrawal, M. Rabinovitch, K. Ambler, et al. 2011. Regulatory T cells limit vascular endothelial injury and prevent pulmonary hypertension. Circ. Res. 109:867-879. http://dx.doi.org/10.1161/CIRCRESAHA.110.236927
59. Thenappan, T., A. Goel, G. Marsboom, Y.H. Fang, P.T. Toth, H.J. Zhang, H. Kajimoto, Z. Hong, J. Paul, C. Wietholt, et al. 2011. A central role for CD68(+) macrophages in hepatopulmonary syndrome. Reversal by macrophage depletion. Am. J. Respir. Crit. Care Med. 183:1080-1091. http://dx.doi.org/10.1164/rccm.201008-1303OC
60. Thorsen, T., S.J. Maerkl, and S.R. Quake. 2002. Microfluidic large-scale integration. Science. 298:580-584. http://dx.doi.org/10.1126/science.1076996
61. Tian, W., X. Jiang, R. Tamosiuniene, Y.K. Sung, J. Qian, G. Dhillon, L. Gera, L. Farkas, M. Rabinovitch, R.T. Zamanian, et al. 2013. Blocking macrophage leukotriene b4 prevents endothelial injury and reverses pulmonary hypertension. Sci. Transl. Med. 5:200ra117. http://dx.doi.org/10.1126/scitranslmed.3006674
62. Toren, A., and A. Nagler. 1998. The implications of granulocyte-monocyte colony-stimulating factor (GM-CSF) in cytotoxicity of bone marrow transplantation. Cytokines Cell. Mol. Ther. 4:199-206.
63. Tourrière, H., K. Chebli, L. Zekri, B. Courselaud, J.M. Blanchard, E. Bertrand, and J. Tazi. 2003. The RasGAP-associated endoribonuclease G3BP assembles stress granules. J. Cell Biol. 160:823-831. http://dx.doi.org/10.1083/jcb.200212128
64. Tuder, R.M., B. Groves, D.B. Badesch, and N.F. Voelkel. 1994. Exuberant endothelial cell growth and elements of inflammation are present in plexiform lesions of pulmonary hypertension. Am. J. Pathol. 144:275-285.
65. Valdembri, D., P.T. Caswell, K.I. Anderson, J.P. Schwarz, I. König, E. Astanina, F. Caccavari, J.C. Norman, M.J. Humphries, F. Bussolino, and G. Serini. 2009. Neuropilin-1/GIPC1 signaling regulates alpha-5beta1 integrin traffic and function in endothelial cells. PLoS Biol. 7:e25. http://dx.doi.org/10.1371/journal.pbio.1000025
66. Vergadi, E., M.S. Chang, C. Lee, O.D. Liang, X. Liu, A. Fernandez-Gonzalez, S.A. Mitsialis, and S. Kourembanas. 2011. Early macrophage recruitment and alternative activation are critical for the later development of hypoxia-induced pulmonary hypertension. Circulation. 123:1986-1995. http://dx.doi.org/10.1161/CIRCULATIONAHA.110.978627
67. Wehner, K.A., S. Schütz, and P. Sarnow. 2010. OGFOD1, a novel modulator of eukaryotic translation initiation factor 2alpha phosphorylation and the cellular response to stress. Mol. Cell. Biol. 30:2006-2016. http://dx.doi.org/10.1128/MCB.01350-09
68. Wilson, D.W., H.J. Segall, L.C. Pan, and S.K. Dunston. 1989. Progressive inflammatory and structural changes in the pulmonary vasculature of monocrotaline-treated rats. Microvasc. Res. 38:57-80. http://dx.doi.org/10.1016/0026-2862(89)90017-4
69. Wu, L., A. Tanimoto, Y. Murata, J. Fan, Y. Sasaguri, and T. Watanabe. 2001. Induction of human matrix metalloproteinase-12 gene transcriptional activity by GM-CSF requires the AP-1 binding site in human U937 monocytic cells. Biochem. Biophys. Res. Commun. 285:300-307. http://dx.doi.org/10.1006/bbrc.2001.5161
70. Yeager, M.E., C.M. Nguyen, D.D. Belchenko, K.L. Colvin, S. Takatsuki, D.D. Ivy, and K.R. Stenmark. 2012. Circulating myeloid-derived suppressor cells are increased and activated in pulmonary hypertension. Chest. 141:944-952.
71. Ying, L., A. Lau, C.M. Alvira, R. West, G.M. Cann, B. Zhou, C. Kinnear, E. Jan, P. Sarnow, M. Van de Rijn, and M. Rabinovitch. 2009. LC3-mediated fibronectin mRNA translation induces fibrosarcoma growth by increasing connective tissue growth factor. J. Cell Sci. 122:1441-1451. http://dx.doi.org/10.1242/jcs.025957
72. Zhu, S.N., M. Chen, J. Jongstra-Bilen, and M.I. Cybulsky. 2009. GMCSF regulates intimal cell proliferation in nascent atherosclerotic lesions. J. Exp. Med. 206:2141-2149. http://dx.doi.org/10.1084/jem.20090866