Mice expressing BMPR2R899X transgene in smooth muscle develop pulmonary vascular lesions

American Journal of Physiology - Lung Cellular and Molecular Physiology

Volumn 295, Issue 5, 2008, Pages

  West, James ^a   Harral, Julie ^b   Lane, Kirk ^a   Deng, Yupu ^c   Ickes, Brian ^b   Crona, Daniel ^b   Albu, Sebastian ^b   Stewart, Duncan ^c   Fagan, Karen ^d  

^a VANDERBILT UNIVERSITY   (United States)

^b UNIVERSITY OF COLORADO   (United States)

^c OTTAWA HOSPITAL RESEARCH INSTITUTE   (Canada)

^d UNIVERSITY OF SOUTH ALABAMA COLLEGE OF MEDICINE   (United States)

Author keywords

Gene expression; Genetically altered mice; Pulmonary circulation and disease

Indexed keywords

BONE MORPHOGENETIC PROTEIN RECEPTOR 2; CD133 ANTIGEN; CD3 ANTIGEN; CD45 ANTIGEN; DOXYCYCLINE; GLYCOPROTEIN; LEUKOCYTE ANTIGEN; MITOGEN ACTIVATED PROTEIN KINASE 1; MITOGEN ACTIVATED PROTEIN KINASE P38; MUTANT PROTEIN; PEPTIDE; SMAD PROTEIN;

ADVENTITIA; ANGIOGENESIS; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; APOPTOSIS; ARTERY MUSCLE; ARTICLE; CONTROLLED STUDY; DNA MICROARRAY; FLUORESCENCE MICROSCOPY; GENE EXPRESSION; GENE MUTATION; HEART RIGHT VENTRICLE PRESSURE; IN VIVO STUDY; LUNG HEMODYNAMICS; MACROPHAGE; MICROANGIOGRAPHY; MOUSE; MUSCLE DEVELOPMENT; MUSCLE FUNCTION; NONHUMAN; NUCLEOTIDE SEQUENCE; PHENOTYPE; PRIORITY JOURNAL; PULMONARY HYPERTENSION; PULMONARY VASCULAR DISEASE; STRESS; SYSTOLIC BLOOD PRESSURE; T LYMPHOCYTE; TRANSGENE; TRANSGENIC MOUSE; ANIMAL; BLOOD PRESSURE; BLOOD VESSEL; CELL CYCLE; CYTOLOGY; ENDOTHELIUM; ENZYMOLOGY; GENE EXPRESSION REGULATION; GENETICS; HEART VENTRICLE; METABOLISM; NEOVASCULARIZATION (PATHOLOGY); PATHOLOGY; PATHOPHYSIOLOGY; PHOSPHORYLATION; SMOOTH MUSCLE; SYSTOLE;

ANIMALS; ANTIGENS, CD; ANTIGENS, CD45; BLOOD PRESSURE; BLOOD VESSELS; BONE MORPHOGENETIC PROTEIN RECEPTORS, TYPE II; CELL CYCLE; ENDOTHELIUM; GENE EXPRESSION REGULATION; GLYCOPROTEINS; HEART VENTRICLES; HYPERTENSION, PULMONARY; MACROPHAGES; MICE; MITOGEN-ACTIVATED PROTEIN KINASE 1; MUSCLE, SMOOTH; MUTANT PROTEINS; NEOVASCULARIZATION, PATHOLOGIC; P38 MITOGEN-ACTIVATED PROTEIN KINASES; PEPTIDES; PHOSPHORYLATION; SMAD PROTEINS; SYSTOLE; T-LYMPHOCYTES; TRANSGENES;

EID: 57049159708     PISSN: 10400605     EISSN: 15221504     Source Type: Journal    
DOI: 10.1152/ajplung.90255.2008     Document Type: Article

References (45)

1. Birkenfeld J, Betz H, Roth D. Identification of cofilin and LIM-domain-containing protein kinase 1 as novel interaction partners of 14-3-3 zeta. Biochem J 369: 45-54, 2003.
2. Chapados R, Abe K, Ihida-Stansbury K, McKean D, Gates AT, Kern M, Merklinger S, Elliott J, Plant A, Shimokawa H, Jones PL. ROCK controls matrix synthesis in vascular smooth muscle cells: coupling vasoconstriction to vascular remodeling. Circ Res 99: 837-844, 2006.
3. Chazova I, Loyd JE, Zhdanov VS, Newman JH, Belenkov Y, Meyrick B. Pulmonary artery adventitial changes and venous involvement in primary pulmonary hypertension. Am J Pathol 146: 389-397, 1995.
4. Chen D, Zhao M, Mundy GR. Bone morphogenetic proteins. Growth Factors 22: 233-241, 2004.
5. Chung AW, Yang HH, Radomski MW, van Breemen C. Long-term doxycycline is more effective than atenolol to prevent thoracic aortic aneurysm in Marfan syndrome through the inhibition of matrix metalloproteinase-2 and -9. Circ Res 102: e73-e85, 2008.
6. Dong J, Grunstein J, Tejada M, Peale F, Frantz G, Liang WC, Bai W, Yu L, Kowalski J, Liang X, Fuh G, Gerber HP, Ferrara N. VEGF-null cells require PDGFR alpha signaling-mediated stromal fibroblast recruitment for tumorigenesis. EMBO J 23: 2800-2810, 2004.
7. Dorfmuller P, Perros F, Balabanian K, Humbert M. Inflammation in pulmonary arterial hypertension. Eur Respir J 22: 358-363, 2003.
8. Fainaru O, Adini I, Benny O, Bazinet L, Pravda E, D'Amato R, Folkman J. Doxycycline induces membrane expression of VE-cadherin on endothelial cells and prevents vascular hyperpermeability. FASEB J. In press.
9. Foletta VC, Lim MA, Soosairajah J, Kelly AP, Stanley EG, Shannon M, He W, Das S, Massague J, Bernard O, Soosairaiah J. Direct signaling by the BMP type II receptor via the cytoskeletal regulator LIMK1. J Cell Biol 162: 1089-1098, 2003.
10. Gene Ontology Consortium. The Gene Ontology (GO) project in 2006. Nucleic Acids Res 34: D322-D326, 2006.
11. Grunig E, Janssen B, Mereles D, Barth U, Borst MM, Vogt IR, Fischer C, Olschewski H, Kuecherer HF, Kubler W. Abnormal pulmonary artery pressure response in asymptomatic carriers of primary pulmonary hypertension gene. Circulation 102: 1145-1150, 2000.
12. Hagen M, Fagan K, Steudel W, Carr M, Lane K, Rodman DM, West J. Interaction of interleukin-6 and the BMP pathway in pulmonary smooth muscle. Am J Physiol Lung Cell Mol Physiol 292: L1473-L1479, 2007.
13. Han C, Belenkaya TY, Khodoun M, Tauchi M, Lin X, Lin X. Distinct and collaborative roles of Drosophila EXT family proteins in morphogen signalling and gradient formation. Development 131: 1563-1575, 2004.
14. Herve P, Humbert M, Sitbon O, Parent F, Nunes H, Legal C, Garcia G, Simonneau G. Pathobiology of pulmonary hypertension. The role of platelets and thrombosis. Clin Chest Med 22: 451-458, 2001.
15. Ichikawa T, Suenaga Y, Koda T, Ozaki T, Nakagawara A. DeltaNp63/BMP-7-dependent expression of matrilin-2 is involved in keratinocyte migration in response to wounding. Biochem Biophys Res Commun 369: 994-1000, 2008.
16. Kim MJ, Park BJ, Kang YS, Kim HJ, Park JH, Kang JW, Lee SW, Han JM, Lee HW, Kim S. Downregulation of FUSE-binding protein and c-myc by tRNA synthetase cofactor p38 is required for lung cell differentiation. Nat Genet 34: 330-336, 2003.
17. Lane KB, Machado RD, Pauciulo MW, Thomson JR, Phillips JA 3rd, Loyd JE, Nichols WC, Trembath RC. Heterozygous germline mutations in BMPR2, encoding a TGF-beta receptor, cause familial primary pulmonary hypertension. The International PPH Consortium. Nat Genet 26: 81-84, 2000.
18. Lawrie A, Waterman E, Southwood M, Evans D, Suntharalingam J, Francis S, Crossman D, Croucher P, Morrell N, Newman C. Evidence of a role for osteoprotegerin in the pathogenesis of pulmonary arterial hypertension. Am J Pathol 172: 256-264, 2008.
19. Li C, Wong WH. Model-based analysis of oligonucleotide arrays: expression index computation and outlier detection. Proc Natl Acad Sci USA 98: 31-36, 2001.
20. Liu D, Wang J, Kinzel B, Mueller M, Mao X, Valdez R, Liu Y, Li E. Dosage-dependent requirement of BMP type II receptor for maintenance of vascular integrity. Blood 110: 1502-1510, 2007.
21. Machado RD, Pauciulo MW, Thomson JR, Lane KB, Morgan NV, Wheeler L, Phillips JA 3rd, Newman J, Williams D, Galiè N, Manes A, McNeil K, Yacoub M, Mikhail G, Rogers P, Corris P, Humbert M, Donnai D, Martensson G, Tranebjaerg L, Loyd JE, Trembath RC, Nichols WC. BMPR2 haploinsufficiency as the inherited molecular mechanism for primary pulmonary hypertension. Am J Hum Genet 68: 92-102, 2001.
22. Machado RD, Rudarakanchana N, Atkinson C, Flanagan JA, Harrison R, Morrell NW, Trembath RC. Functional interaction between BMPR-II and Tctex-1, a light chain of Dynein, is isoform-specific and disrupted by mutations underlying primary pulmonary hypertension. Hum Mol Genet 12: 3277-3286, 2003.
23. Monteiro RM, de Sousa Lopes SM, Korchynskyi O, ten Dijke P, Mummery CL. Spatio-temporal activation of Smad1 and Smad5 in vivo: monitoring transcriptional activity of Smad proteins. J Cell Sci 117: 4653-4663, 2004.
24. Moses MA, Harper J, Folkman J. Doxycycline treatment for lymphangioleiomyomatosis with urinary monitoring for MMPs. N Engl J Med 354: 2621-2622, 2006.
25. Murray CD. The physiological principle of ninimum work: I. The vascular system and the cost of blood volume. Proc Natl Acad Sci USA 12: 207-214, 1926.
26. Nishihara A, Watabe T, Imamura T, Miyazono K. Functional heterogeneity of bone morphogenetic protein receptor-II mutants found in patients with primary pulmonary hypertension. Mol Biol Cell 13: 3055-3063, 2002.
27. Rudarakanchana N, Flanagan JA, Chen H, Upton PD, Machado R, Patel D, Trembath RC, Morrell NW. Functional analysis of bone morphogenetic protein type II receptor mutations underlying primary pulmonary hypertension. Hum Mol Genet 11: 1517-1525, 2002.
28. Ryter SW, Choi AM. Heme oxygenase-1: redox regulation of a stress protein in lung and cell culture models. Antioxid Redox Signal 7: 80-91, 2005.
29. Shimokawa H, Takeshita A. Rho-kinase is an important therapeutic target in cardiovascular medicine. Arterioscler Thromb Vasc Biol 25: 1767-1775, 2005.
30. Sil P, Gupta S, Young D, Sen S. Regulation of myotrophin gene by pressure overload and stretch. Mol Cell Biochem 262: 79-89, 2004.
31. Singleton PA, Salgia R, Moreno-Vinasco L, Moitra J, Sammani S, Mirzapoiazova T, Garcia JG. CD44 regulates hepatocyte growth factor-mediated vascular integrity. Role of c-Met, Tiam1/Rac1, dynamin 2, and cortactin. J Biol Chem 282: 30643-30657, 2007.
32. Song Y, Coleman L, Shi J, Beppu H, Sato K, Walsh K, Loscalzo J, Zhang YY. Inflammation, endothelial injury, and persistent pulmonary hypertension in heterozygous BMPR2-mutant mice. Am J Physiol Heart Circ Physiol 295: H677-H690, 2008.
33. Tada Y, Majka S, Carr M, Harral J, Crona D, Kuriyama T, West J. Molecular effects of loss of BMPR2 signaling in smooth muscle in a transgenic mouse model of PAH. Am J Physiol Lung Cell Mol Physiol 292: L1556-L1563, 2007.
34. Taraseviciene-Stewart L, Kasahara Y, Alger L, Hirth P, Mc Mahon G, Waltenberger J, Voelkel NF, Tuder RM. Inhibition of the VEGF receptor 2 combined with chronic hypoxia causes cell death-dependent pulmonary endothelial cell proliferation and severe pulmonary hypertension. FASEB J 15: 427-438, 2001.
35. Vieillard-Baron A, Frisdal E, Eddahibi S, Deprez I, Baker AH, Newby AC, Berger P, Levame M, Raffestin B, Adnot S, d'Ortho MP. Inhibition of matrix metalloproteinases by lung TIMP-1 gene transfer or doxycycline aggravates pulmonary hypertension in rats. Circ Res 87: 418-425, 2000.
36. West J, Fagan K, Steudel W, Fouty B, Lane K, Harral J, Hoedt-Miller M, Tada Y, Ozimek J, Tuder R, Rodman DM. Pulmonary hypertension in transgenic mice expressing a dominant-negative BMPRII gene in smooth muscle. Circ Res 94: 1109-1114, 2004.
37. Wong WK, Knowles JA, Morse JH. Bone morphogenetic protein receptor type II C-terminus interacts with c-Src: implication for a role in pulmonary arterial hypertension. Am J Respir Cell Mol Biol 33: 438-446, 2005.
38. World CJ, Yamawaki H, Berk BC. Thioredoxin in the cardiovascular system. J Mol Med 84: 997-1003, 2006.
39. Yang X, Lee PJ, Long L, Trembath RC, Morrell NW. BMP4 induces HO-1 via a Smad-independent, p38MAPK-dependent pathway in pulmonary artery myocytes. Am J Respir Cell Mol Biol 37: 598-605, 2007.
40. Yang X, Long L, Southwood M, Rudarakanchana N, Upton PD, Jeffery TK, Atkinson C, Chen H, Trembath RC, Morrell NW. Dysfunctional Smad signaling contributes to abnormal smooth muscle cell proliferation in familial pulmonary arterial hypertension. Circ Res 96: 1053-1063, 2005.
41. Yoshioka J, Imahashi K, Gabel SA, Chutkow WA, Burds AA, Gannon J, Schulze PC, MacGillivray C, London RE, Murphy E, Lee RT. Targeted deletion of thioredoxin-interacting protein regulates cardiac dysfunction in response to pressure overload. Circ Res 101: 1328-1338, 2007.
42. Young KA, Ivester C, West J, Carr M, Rodman DM. BMP signaling controls PASMC KV channel expression in vitro and in vivo. Am J Physiol Lung Cell Mol Physiol 290: L841-L848, 2006.
43. Zaheer A, Zaheer S, Sahu SK, Yang B, Lim R. Reduced severity of experimental autoimmune encephalomyelitis in GMF-deficient mice. Neurochem Res 32: 39-47, 2007.
44. Zakrzewicz A, Hecker M, Marsh LM, Kwapiszewska G, Nejman B, Long L, Seeger W, Schermuly RT, Morrell NW, Morty RE, Eickelberg O. Receptor for activated C-kinase 1, a novel interaction partner of type II bone morphogenetic protein receptor, regulates smooth muscle cell proliferation in pulmonary arterial hypertension. Circulation 115: 2957-2968, 2007.
45. Zhong S, Li C, Wong WH. ChipInfo: software for extracting gene annotation and gene ontology information for microarray analysis. Nucleic Acids Res 31: 3483-3486, 2003.