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LUH Shi-ping, CHIANG Chi-huei. Acute lung injury/acute respiratory distress syndrome (ALI/ARDS): the mechanism, present strategies and future perspectives of therapies[J]. Journal of Zhejiang University Science B, 2007, 8(1): 60-69.
@article{title="Acute lung injury/acute respiratory distress syndrome (ALI/ARDS): the mechanism, present strategies and future perspectives of therapies",
author="LUH Shi-ping, CHIANG Chi-huei",
journal="Journal of Zhejiang University Science B",
volume="8",
number="1",
pages="60-69",
year="2007",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.2007.B0060"
}
%0 Journal Article
%T Acute lung injury/acute respiratory distress syndrome (ALI/ARDS): the mechanism, present strategies and future perspectives of therapies
%A LUH Shi-ping
%A CHIANG Chi-huei
%J Journal of Zhejiang University SCIENCE B
%V 8
%N 1
%P 60-69
%@ 1673-1581
%D 2007
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.2007.B0060
TY - JOUR
T1 - Acute lung injury/acute respiratory distress syndrome (ALI/ARDS): the mechanism, present strategies and future perspectives of therapies
A1 - LUH Shi-ping
A1 - CHIANG Chi-huei
J0 - Journal of Zhejiang University Science B
VL - 8
IS - 1
SP - 60
EP - 69
%@ 1673-1581
Y1 - 2007
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.2007.B0060
Abstract: acute lung injury/acute respiratory distress syndrome (ALI/ARDS), which manifests as non-cardiogenic pulmonary edema, respiratory distress and hypoxemia, could be resulted from various processes that directly or indirectly injure the lung. Extensive investigations in experimental models and humans with ALI/ARDS have revealed many molecular mechanisms that offer therapeutic opportunities for cell or gene therapy. Herein the present strategies and future perspectives of the treatment for ALI/ARDS, include the ventilatory, pharmacological, as well as cell therapies.
[1] Ali, N.N., Edgar, A.J., Samadikuchaksaraei, A., Timson, C.M., Romanska, H.M., Polak, J.M., Bishop, A.E., 2002. Derivation of type II alveolar epithelial cells from murine embryonic stem cells. Tissue Eng., 8(4):541-550.
[2] Archer, S., Rich, S., 2000. Primary pulmonary hypertension: a vascular biology and translational research “work in progress”. Circulation, 102(22):2781-2791.
[3] Asahara, T., Murohara, T., Sullivan, A., Silver, M., van der Zee, R., Li, T., Witzenbichler, B., Schatteman, G., Isner, J.M., 1997. Isolation of putative progenitor endothelial cells for angiogenesis. Science, 275(5302):964-967.
[4] Avery, R.K., 1999. Special considerations regarding CMV in lung transplantation. Transpl. Infect. Dis., 1(Suppl. 1):13-18.
[5] Bernard, G.R., Artigas, A., Brigham, K.L., Carlet, J., Falke, K., Hudson, L., Lamy, M., Legall, J.R., Morris, A., Spragg, R., 1994. The American-European consensus conference on ARDS: definitions, mechanisms, relevant outcomes, and clinical trial coordination. Am. J. Respir. Crit. Care Med., 149(3 Pt 1):818-824.
[6] Brazelton, T.R., Rossi, F.M., Keshet, G.I., Blau, H.M., 2000. From marrow to brain: expression of neuronal phenotypes in adult mice. Science, 290(5497):1775-1779.
[7] Breen, P.H., Schumacker, P.T., Hedenstierna, G., Ali, J., Wagner, P.D., Wood, L.D., 1982. How does increased cardiac output increase shunt in pulmonary edema? J. Appl. Physiol., 53(5):1273-1280.
[8] Brown, L.M., Rannels, S.R., Rannels, D.E., 2001. Implications of post-pneumonectomy compensatory lung growth in pulmonary physiology and disease. Respir. Res., 2(6):340-347.
[9] Brun-Buisson, C., Doyon, F., Carlet, J., Dellamonica, P., Gouin, F., Lepoutre, A., Mercier, J.C., Offenstadt, G., Regnier, B., 1995. Incidence, risk factors, and outcome of severe sepsis and septic shock in adults: a multicenter prospective study in intensive care units. French ICU Group for Severe Sepsis. JAMA, 274(12):968-974.
[10] Burnham, E.L., Taylor, W.R., Quyyumi, A.A., Rojas, M., Brigham, K.L., Moss, M., 2005. Increased circulating endothelial progenitor cells are associated with survival in acute lung injury. Am. J. Respir. Crit. Care Med., 172(7):854-860.
[11] Campbell, A.I., Kuliszewski, M.A., Stewart, D.J., 1999. Cell-based gene transfer to the pulmonary vasculature: endothelial nitric oxide synthase overexpression inhibits moncrotaline-induced pulmonary hypertension. Am. J. Respir. Cell Mol. Biol., 21(5):567-575.
[12] Campbell, A.I., Zhao, Y., Sandhu, R., Stewart, D.J., 2001. Cell-based gene transfer of vascular endothelial growth factor attenuates monocrotamine-induced pulmonary hypertension. Circulation, 104(18):2242-2248.
[13] Chan, A., Allen, R., 2004. Bronchiolitis obliterans: an update. Curr. Opin. Pulm. Med., 10(2):133-141.
[14] Chaparro, C., Kesten, S., 1997. Infections in lung transplant recipients. Clin. Chest Med., 18(2):339-351.
[15] Coraux, C., Hilmi, C., Rouleau, M., Spadafora, A., Hinnrasky, J., Ortonne, J.P., Dani, C., Aberdam, D., 2003. Reconstituted skin from murine embryonic stem cells. Curr. Biol., 13(10):849-853.
[16] Coraux, C., Nawrocki-Raby, B., Hinnrasky, J., Kileztky, C., Gaillard, D., Dani, C., Puchelle, E., 2004. Embryonic stem cells generate airway epithelial tissue. Am. J. Respir. Cell Mol. Biol., 32(2):87-95.
[17] Crouser, E.D., Dorinsky, P.M., 1994. Gastrointestinal tract dysfunction in critical illness: pathophysiology and interaction with acute lung injury in adult respiratory distress syndrome/multiple organ dysfunction syndrome. N. Horiz., 2(4):476-487.
[18] Davidson, T.A., Caldwell, E.S., Curtis, J.R., Hudson, L.D., Steinberg, K.P., 1999. Reduced quality of life in survivors of acute respiratory distress syndrome compared with critically ill control patients. JAMA, 281(4):354-360.
[19] Deitch, E.A., 1992. Multiple organ failure: pathogenesis and potential future therapy. Ann. Surg., 216(2):117-134.
[20] Dupont, H., LeCorre, R., Fierobe, L., Cheval, C., Moine, P., Timsit, J.F., 1999. Efficacy of inhaled nitric oxide as rescue therapy during severe ARDS: survival and factors associated with the first responses. J. Crit. Care, 14(3):107-113.
[21] Eglitis, M.A., Mezey, E., 1997. Hematopoietic cells differentiate into both microglia in the brains of adult mice. Proc. Natl. Acad. Sci. USA, 94(8):4080-4085.
[22] Evans, M.J., Kaufman, M.H., 1981. Establishment in culture of pluripotential cells from mouse embryos. Nature, 292(5819):154-156.
[23] Ezri, T., Kunichezky, S., Eliraz, A., Soroker, D., Halperin, D., Schattner, A., 1994. Bronchiolitis obliterans-current concepts. Q. J. Med., 87(1):1-10.
[24] Ferrari, G., Cusella-De Angelis, G., Coletta, M., Paolucci, E., Stornaiuolo, A., Cossu, G., Mavilio, F., 1998. Muscle regeneration by bone marrow derived myogenic progenitors. Science, 279(5356):1528-1530.
[25] Fowler, A.A., Hamman, R.F., Good, J.T., Benson, K.N., Baird, M., Eberle, D.J., Petty, T.L., Hyers, T.M., 1983. Adult respiratory distress syndrome: risk with common predisposition. Ann. Intern. Med., 98(5 Pt 1):593-597.
[26] Frost, A.E., 2002. Bronchiolitis obliterans: the Achilles heel of lung transplantation. Veth. K. Acad. Geneeskd. Belg., 64(5):303-319.
[27] Gao, Z., McAlister, V.C., Williams, G.M., 2001. Repopulation of liver endothelium by bone-marrow-derived cells. Lancet, 357(9260):932-933.
[28] Gattinoni, L., Pelosi, P., Vitale, G., Pesenti, A., D'Andrea, L., Mascheroni, D., 1991. Body position changes redistribute lung computed tomographic density in patient with acute respiratory failure. Anesthesiology, 74(1):15-23.
[29] Gill, M., Dias, S., Hattori, K., Rivera, M.L., Hicklin, D., Witte, L., Girardi, L., Yurt, R., Himel, H., Rafii, S., 2001. Vascular trauma induces rapid but transient mobilization of VEGFR2(+) AC133(+) endothelial precursor cells. Circ. Res., 88(2):167-174.
[30] Goris, R.J., te Bockhorst, T.P., Nuytinck, J.K., Gimbrere, J.S., 1985. Multiple organ failure: generalized autodestructive inflammation? Arch. Surg., 120(10):1109-1115.
[31] Grimm, P.C., Nickerson, P., Jeffery, J., Savani, R.C., Gough, J., McKenna, R.M., Stem, E., Rush, D.N., 2001. Neointimal and tubulointerstitial infiltration by recipient mesenchymal cells in chronic renal allograft rejection. N. Engl. J. Med., 345(2):93-97.
[32] Grove, J.E., Lutzko, C., Poller, J., Hengariu, O., Theise, N.D., Kohn, D.B., Krause, D.S., 2002. Marrow-derived cells as vehicles for delivery of gene therapy to pulmonary epithelium. Am. J. Respir. Cell Mol. Biol., 27(6):645-651.
[33] Harari, A., Zimmerli, S.C., Pantaleo, G., 2004. Cytomegalovirus (CMV) specific cellular immune responses. Hum. Immunol., 65(5):500-506.
[34] Hooper, R.G., 1991. ARDS: inflammation, infections, and corticosteroids. Chest, 100(4):889-890.
[35] Jones, E.A., Tosh, D., Wilson, D.I., Lindsay, S., Forrester, L.M., 2002. Hepatic differentiation of murine embryonic stem cells. Exp. Cell Res., 272(1):15-22.
[36] Keller, G.M., 1995. In vitro differentiation of embryonic stem cells. Curr. Opin. Cell Biol., 7(6):862-869.
[37] Kitamura, K., Kangawa, K., Kawamoto, M., Ichiki, Y., Nakamura, S., Matsuo, H., Eto, T., 1993. Adrenomedullin: a novel hypotensive peptide isolated from human pheochromocytoma. Biochem. Biophy. Res. Commun., 192(2):553-560.
[38] Klepetko, W., Laufer, G., Kocher, A., 2004. Thoracic transplantation and stem cell therapy. Eur. J. Cardiothorac. Surg., 26(Suppl. 1):S57-S58.
[39] Kocher, A.A., Schuster, M.D., Szabolcs, M.J., Takuma, S., Burkhoff, D., Wang, J., Homma, S., Edwards, N.M., Itescu, S., 2001. Neovascularization of ischemic myocardium by human bone-marrow-derived angioblasts prevents cardiomyocyte apoptosis, reduces remodeling and improves cardiac function. Nat. Med., 7(4):430-436.
[40] Kollef, M.H., Schuster, D., 1996. Acute respiratory distress syndrome. DM, 42(5):266-326.
[41] Korbling, M., Katz, R.L., Khanna, A., Ruifrok, A.C., Rondon, G., Albitar, M., Champlin, R.E., Estrov, Z., 2002. Hepatocytes and epithelial cells of donor origin in recipients of peripheral blood stem cells. N. Engl. J. Med., 346(10):738-746.
[42] Kotton, D.N., Ma, B.Y., Cardoso, W.V., Sanderson, E.A., Summer, R.S., Williams, M.C., Fine, A., 2001. Bone marrow-derived cells progenitors of lung alveolar epithelium. Development, 128(24):5181-5188.
[43] Krause, D.S., Theise, N.D., Collector, M.I., Henegariu, O., Hwang, S., Gardner, R., Neutzel, S., Sharkis, S.J., 2001. Multi-organ, multilineage engraftment by a single bone marrow derived stem cells. Cell, 105(3):369-377.
[44] Kubo, H., 2005. Is cell therapy in acute lung injury a realistic dream? Am. J. Respir. Crit. Care Med., 172(7):794-795.
[45] Kuebler, W.M., Ying, X., Singh, B., Issekutz, A.C., Bhattacharya, J., 1999. Pressure is proinflammatory in lung venular capillaries. J. Clin. Invest., 104(4):495-502.
[46] Kuebler, W.M., Parthasarathi, K., Wang, P.M., Bhattacharya, J., 2000. A novel signaling mechanism between gas and blood compartments of the lung. J. Clin. Invest., 105(7):905-913.
[47] Kugathasan, L., Duty, A.E., Zhao, Y.D., Deng, Y., Robb, M.J., Keshavjee, S., Stewart, D.J., 2005. Role of angiopoitin-1 in experimental and human pulmonary arterial hypertension. Chest, 128(6_suppl.):633S-642S.
[48] Lagasse, E., Connors, H., Al-Dhalimy, M., Reitsma, M., Dohse, M., Osborne, L., Wang, X., Finegold, M., Weissman, I.L., Grompe, M., 2000. Purified hematopoietic stem cells can differentiate into hepatocytes in vivo. Nat. Med., 6(11):1229-1234.
[49] Leach, C.L., Fuhrman, B.P., Morin, F.C.3rd, Rath, M.G., 1993. Perfluorocarbon-associated gas exchange (partial liquid ventilation) in respiratory distress syndrome. A prospective randomized, controlled study. Crit. Care Med., 21(9):1270-1278.
[50] Lessard, M.R., 1996. New concepts in mechanical ventilation for ARDS. Can. J. Anesth., 43(5 Pt 2):R50-R54.
[51] Luhr, O.R., Antonsen, K., Karlsson, M., Aardal, S., Thorsteinsson, A., Frostell, C.G., Bonde, J., 1999. Incidence and mortality after acute respiratory failure and acute respiratory distress syndrome in Sweden, Denmark, and Iceland. The ARF study group. Am. J. Respir. Crit. Care Med., 159(6):1849-1861.
[52] Lumelsky, N., Blondel, O., Laeng, P., Belassco, I., Ravin, R., McKay, R., 2001. Differentiation of embryonic stem cells to insulin-secreting structures similar to pancreatic islets. Science, 292(5520):1389-1394.
[53] Martin, G.R., 1981. Isolation of a pluripotent cell line from early mouse embryos cultured in medium conditioned by teratocarcinoma stem cells. Proc. Natl. Acad. Sci. USA, 78(12):7634-7638.
[54] Matthay, M.A., Wierner-Kronish, J.P., 1990. Intact epithelial barrier function is critical for the resolution of alveolar edema in humans. Am. Rev. Respir. Dis., 142(6 Pt 1):1250-1257.
[55] Matuschak, G.M., 1994. Liver-lung interactions in critical illness. N. Horiz., 2(2):488-504.
[56] Meduri, G.U., Chinn, A.J., Leeper, K.V., Wunderink, R.G., Tolley, E., Winer-Muram, H.T., Khare, V., Eltorky, M., 1994. Corticosteroid rescue treatment of progressive fibroproliferation in late ARDS. Chest, 105(5):1516-1527.
[57] Milberg, J.A., Davis, D.R., Steinberg, K.P., Hudson, L.D., 1995. Improved survival of patients with acute respiratory distress syndrome (ARDS). JAMA, 273(4):306-309.
[58] Milne, E.N.C., Pistolesi, M., Miniati, M., Giuntini, C., 1985. The radiologic distinction of cardiogenic and non-cardiogenic edema. Am. J. Roentgenol., 144(5):879.
[59] Moss, P., Khan, N., 2004. CD8(+) T cell immunity to cytomegalovirus. Hum. Immunol., 65(5):456-464.
[60] Munford, R.S., Pugin, J., 2001. Normal responses to injury prevent systemic inflammation and can be immunosuppressive. Am. J. Respir. Crit. Care Med., 163(2):316-321.
[61] Nagaya, N., Kangawa, K., Kanda, M., Uematsu, M., Horio, T., Fukuyama, N., Hino, J., Harada-Shiba, M., Okumura, H., Tabata, Y., et al., 2003a. Hybrid cell-gene therapy for pulmonary hypertension based on phagocytosing action of entothelial progenitor cells. Circulation, 108(7):889-895.
[62] Nagaya, N., Kanda, M., Horio, T., Kangawa, K., Uematsu, M., Fukuyama, N., Hino, J., Harada-Shiba, M., Okumura, H., Tabata, Y., et al., 2003b. Hybrid cell-gene therapy for pulmonary hypertension based on phagocytoing action of endothelial progenitor cells. Circulation, 108(7):889-896.
[63] Odorico, J.S., Kaufman, D.S., Thomson, J.A., 2001. Multilineage differentiation from human embryonic stem cell lines. Stem Cells, 19(3):193-204.
[64] Otto, W.R., 2002. Lung epithelial stem cells. J. Pathol., 197(4):527-535.
[65] Paradis, I., Yousem, S., Griffith, B., 1993. Airway obstruction and bronchiolitis obliterans after lung transplantation. Clin. Chest Med., 14(4):751-763.
[66] Paulson, T.E., Spear, R.M., Silva, P.D., Peterson, B.M., 1996. High-frequency pressure-control ventilation with high positive end-expiratory pressure in children with acute respiratory distress syndrome. J. Pediatr., 129(4):566-578.
[67] Petersen, B.E., Bowen, W.C., Patrene, K.D., Mars, W.M., Sullivan, A.K., Murase, N., Boggs, S.S., Greengerger, J.S., Goff, J.P., 1999. Bone marrow as a potential source of hepatic oval cells. Science, 284(5417):1168-1170.
[68] Pistolesi, M., Milne, E.W.C., Miniati, M., Giuntini, C., 1984. The vascular pedicle of the heart and the vena azygos. Part II: Acquired heart disease. Radiology, 152(1):9.
[69] Poulsom, R., Alison, M.R., Forbes, S.J., Wright, N.A., 2002. Adult stem cell plasticity. J. Pathol., 197(4):441-456.
[70] Ralph, D.D., Robertson, H.T., Weaver, L.J., Hlastala, M.P., Carrico, C.J., Hudson, L.D., 1985. Distribution of ventilation and perfusion during positive end-expiratory pressure in the adult respiratory distress syndrome. Am. Rev. Respir. Dis., 131(1):54.
[71] Rossaint, R., Gerlach, H., Schmidt-Ruhnke, H., Pappert, D., Lewandowski, K., Steudel, W., Falke, K., 1995. Efficacy of inhaled nitric oxide in patients with severe ARDS. Chest, 107(4):1107-1115.
[72] Roupie, E., Dambrosio, M., Servillo, G., Mentec, H., el Atrous, S., Beydon, L., Brun-Buisson, C., Lemaire, F., Brochard, L., 1995. Titration of tidal volume and induced hypercapnia in acute respiratory distress syndrome. Am. J. Respir. Crit. Care Med., 152(1):121-128.
[73] Sanajder, J.I., 1999. Strategies to increase alveolar epithelial fluid removal in the injured lung. Am. J. Respir. Crit. Care Med., 160(5 Pt 1):1441-1442.
[74] Schumacker, P.T., Samsel, R.W., 1990. Oxygen supply and consumption in the adult respiratory distress syndrome. Clin. Chest Med., 11(4):715-722.
[75] Sivan, Y., Mor, C., al-Jundi, S., Newth, C.J., 1990. Adult respiratory distress syndrome in severely neutropenic children. Pediatr. Pulmonol., 8(2):104-108.
[76] Spencer, H., Jaffe, A., 2004. The potential for stem cell therapy in cystic fibrosis. J. R. Soc. Med., 97(Suppl. 44):52-56.
[77] Sprung, C.L., Long, W.M., Marcial, E.H., Schein, R.M., Parker, R.E., Shomer, T., Brigham, K.L., 1987. Distribution of proteins in pulmonary edema. The value of fractional concentration. Am. Rev. Respir. Dis., 136(4):957.
[78] St. John, R.C., Mizer, L.A., Weisbrode, S.E., Dorinsky, P.M., 1991. Increased protein permeability in the cat ileum after acid aspiration-induced acute lung injury. Evidence for systemic endothelial injury. Am. Rev. Respir. Dis., 143(5):A805.
[79] Slutsky, A.S., Tremblay, L.N., 1998. Multiple system organ failure: is mechanical ventilation a contributing factor? Am. J. Respir. Crit. Care Med., 157(6 Pt 1):1721-1725.
[80] Suratt, B.T., Cool, C.D., Serls, A., Chen, L., Varella-Garcia, M., Shpall, E.J., Brown, K.K., Worthen, G.S., 2003. Human pulmonary chimerism after hematopoietic stem cell transplantation. Am. J. Respir. Crit. Care Med., 168(3):318-322.
[81] Sydow, M., Burchardi, H., Ephraim, E., Zielmann, S., Crozier, T.A., 1994. Long-term effects of two different ventilatory modes on oxygenation in acute lung injury. Comparison of airway pressure release ventilation and volume controlled inverse ratio ventilation. Am. J. Respir. Crit. Care Med., 149(6):1550-1556.
[82] Takahashi, T., Kalka, C., Masuda, H., Chen, D., Silver, M., Kearney, M., Magner, M., Isner, J.M., Asahara, T., 1999. Ischemia- and cytokine-induced mobilization of bone marrow-derived endothelial progenitor cells for neovascularization. Nat. Med., 5(4):434-438.
[83] Tharratt, R.S., Allen, R.P., Albertson, T.E., 1988. Pressure controlled inverse ratio ventilation in severe adult respiratory failure. Chest, 94(4):755-762.
[84] Theise, N.D., Nimmakayalu, M., Cardner, R., Illei, P.B., Morgan, G., Teperman, L., Henegariu, O., Krause, D.S., 2000. Liver form bone marrow in humans. Hepatology, 32(1):11-16.
[85] Tomashefsk, J.F., 1990. Pulmonary pathology of the adult respiratory distress syndrome. Clin. Chest Med., 11(4):593-619.
[86] Tuchschmidt, J., Fried, J., Astiz, M., Rackow, E., 1992. Elevation of cardiac output and oxygen delivery improves outcome in septic shock. Chest, 102(1):216-220.
[87] Walmrath, D., Gunther, A., Ghofrani, H.A., Schermuly, R., Schneider, T., Grimminger, F., Seeger, W., 1996. Bronchoscopic surfactant administration in patients with severe adult respiratory distress syndrome. Am. J. Respir. Crit. Care Med., 154(1):57-62.
[88] Ware, L.B., Matthay, M.A., 2000. The acute respiratory distress syndrome. N. Engl. J. Med., 342(18):1334-1349.
[89] Ware, L.B., Matthay, M.A., 2002. Keratinocyte and hepatocyte growth factors in the lung: roles in lung development, inflammation and repair. Am. J. Physiol. Lung. Cell Mol. Physiol., 282(5):L924-L940.
[90] Windsor, A.C., Walsh, C.J., Mullen, P.G., Cook, D.J., Fisher, B.J., Blocher, C.R., Leeper-Woodford, S.K., Sugerman, H.J., Fowler, A.A.3rd, 1993. Tumor necrosis factor-alpha blockade prevents neutrophil CD18 receptor upregulation and attenuates acute lung injury in porcine sepsis without inhibition of neutrophil oxygen radical generation. J. Clin. Invest., 91(4):1459-1468.
[91] Yamada, M., Kubo, H., Kobayashi, S., Ishizawa, K., Numasaki, M., Ueda, S., Suzuki, T., Sasaki, H., 2004. Bone marrow derived progenitor cells are important for lung repair after lipopolysaccharide-induced lung injury. J. Immuol., 172(2):1266-1272.
[92] Zapol, W.M., Trelstad, R.L., Coffey, J.W., Tsai, I., Salvador, R.A., 1979a. Pulmonary fibrosis in severe acute respiratory failure. Am. Rev. Respir. Dis., 119(4):547-554.
[93] Zapol, W.M., Snider, M.T., Hill, J.D., Fallat, R.J., Bartlett, R.H., Edmunds, L.H., Morris, A.H., Peirce, E.C.2nd, Thomas, A.N., Proctor, H.J., et al., 1979b. Extracorporeal membrane oxygenation in severe acute respiratory failure. JAMA, 242(20):2193-2196.
[94] Zhao, Y.D., Campbell, A.I., Robb, M., Ng, D., Stewart, D.J., 2003. Protective role of angiopoitin-1 in experimental pulmonary hypertension. Circ. Res., 92(9):984-991.
[95] Zimmerman, G.A., McIntyre, T.M., Prescott, S.M., 1996. Adhesion and signaling in vascular cell-cell interactions. J. Clin. Invest., 98(8):1699-1702.
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