Endothelial-to-mesenchymal transition contributes to cardiac fibrosis

Nature Medicine

Volumn 13, Issue 8, 2007, Pages 952-961

  Zeisberg, Elisabeth M ^a   Tarnavski, Oleg ^b   Zeisberg, Michael ^a   Dorfman, Adam L ^c   McMullen, Julie R ^a   Gustafsson, Erika ^d   Chandraker, Anil ^c   Yuan, Xueli ^c   Pu, William T ^c   Roberts, Anita B ^e   Neilson, Eric G ^f   Sayegh, Mohamed H ^c   Izumo, Seigo ^b   Kalluri, Raghu ^a,g  

^a HARVARD MEDICAL SCHOOL   (United States)

^b NOVARTIS INSTITUTES FOR BIOMEDICAL RESEARCH   (United States)

^c BOSTON CHILDREN S HOSPITAL   (United States)

^d LUND UNIVERSITY   (Sweden)

^e NATIONAL CANCER INSTITUTE   (United States)

^f VANDERBILT UNIVERSITY   (United States)

^g HARVARD MIT DIVISION OF HEALTH SCIENCES AND TECHNOLOGY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

OSTEOGENIC PROTEIN 1; RECOMBINANT OSTEOGENIC PROTEIN 1; TRANSFORMING GROWTH FACTOR BETA1;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CHRONIC GRAFT REJECTION; CONTROLLED STUDY; ENDOTHELIUM CELL; EXTRACELLULAR MATRIX; FIBROBLAST; HEART MUSCLE; HEART MUSCLE FIBROSIS; HUMAN; HUMAN CELL; MICROVASCULATURE; MOUSE; NONHUMAN; PRIORITY JOURNAL;

ANIMALS; BONE MARROW CELLS; BONE MORPHOGENETIC PROTEINS; CELL DIFFERENTIATION; CELL LINE; CELLS, CULTURED; CHRONIC DISEASE; ENDOMYOCARDIAL FIBROSIS; ENDOTHELIAL CELLS; HUMANS; MESENCHYMAL STEM CELLS; MESODERM; MICE; MICE, TRANSGENIC; TRANSFORMING GROWTH FACTOR BETA; TRANSFORMING GROWTH FACTOR BETA1;

EID: 34547676391     PISSN: 10788956     EISSN: 1546170X     Source Type: Journal    
DOI: 10.1038/nm1613     Document Type: Article

References (50)

1. Jalil, J.E. et al. Fibrillar collagen and myocardial stiffness in the intact hypertrophied rat left ventricle. Circ. Res. 64, 1041-1050 (1989).
2. Kass, D.A., Bronzwaer, J.G. & Paulus, W.J. What mechanisms underlie diastolic dysfunction in heart failure? Circ. Res. 94, 1533-1542 (2004).
3. Vasan, R.S. & Benjamin, E.J. Diastolic heart failure - no time to relax. N. Engl. J. Med. 344, 56-59 (2001).
4. Weber, K.T. Monitoring tissue repair and fibrosis from a distance. Circulation 96, 2488-2492 (1997).
5. Maric, C., Ryan, G.B. & Alcorn, D. Embryonic and postnatal development of the rat renal interstitium. Anat. Embryol. (Berl.) 195, 503-514 (1997).
6. Lang, H. & Fekete, D.M. Lineage analysis in the chicken inner ear shows differences in clonal dispersion for epithelial, neuronal, and mesenchymal cells. Dev. Biol. 234, 120-137 (2001).
7. Iwano, M. et al. Evidence that fibroblasts derive from epithelium during tissue fibrosis. J. Clin. Invest. 110, 341-350 (2002).
8. Eisenberg, L.M. & Markwald, R.R. Molecular regulation of atrioventricular valvuloseptal morphogenesis. Circ. Res. 77, 1-6 (1995).
9. Liebner, S. et al. Beta-catenin is required for endothelial-mesenchymal transformation during heart cushion development in the mouse. J. Cell Biol. 166, 359-367 (2004).
10. Nakajima, Y., Yamagishi, T., Hokari, S. & Nakamura, H. Mechanisms involved in valvuloseptal endocardial cushion formation in early cardiogenesis: roles of transforming growth factor (TGF)-beta and bone morphogenetic protein (BMP). Anat. Rec. 258, 119-127 (2000).
11. Boyer, A.S. et al. TGFβ2 and TGFβ3 have separate and sequential activities during epithelial-mesenchymal cell transformation in the embryonic heart. Dev. Biol. 208, 530-545 (1999).
12. Camenisch, T.D. et al. Temporal and distinct TGFβ ligand requirements during mouse and avian endocardial cushion morphogenesis. Dev. Biol. 248, 170-181 (2002).
13. 1. Mol. Genet. Metab. 71, 418-435 (2000).
14. Ramsdell, A.F. et al. Identification of an autocrine signaling pathway that amplifies induction of endocardial cushion tissue in the avian heart. Acta Anat. 162, 1-15 (1998).
15. Gustafsson, E., Brakebusch, C., Hietanen, K. & Fassler, R. Tie-1-directed expression of Cre recombinase in endothelial cells of embryoid bodies and transgenic mice. J. Cell Sci. 114, 671-676 (2001).
16. Mao, X., Fujiwara, Y. & Orkin, S.H. Improved reporter strain for monitoring Cre recombinase-mediated DNA excisions in mice. Proc. Natl. Acad. Sci. USA 96, 5037-5042 (1999).
17. Korhonen, J., Polvi, A., Partanen, J. & Alitalo, K. The mouse tie receptor tyrosine kinase gene: expression during embryonic angiogenesis. Oncogene 9, 395-403 (1994).
18. Rafii, S. & Lyden, D. Therapeutic stem and progenitor cell transplantation for organ vascularization and regeneration. Nat. Med. 9, 702-712 (2003).
19. Hocht-Zeisberg, E. et al. Cellular repopulation of myocardial infarction in patients with sex-mismatched heart transplantation. Eur. Heart J. 25, 749-758 (2004).
20. Kuwahara, F. et al. Transforming growth factor-beta function blocking prevents myocardial fibrosis and diastolic dysfunction in pressure-overloaded rats. Circulation 106, 130-135 (2002).
21. Lebrin, F. et al. TGF-beta receptor function in the endothelium. Cardiovasc. Res. 65, 599-608 (2005).
22. Yang, X. et al. Targeted disruption of SMAD3 results in impaired mucosal immunity and diminished T cell responsiveness to TGF-beta. EMBO J. 18, 1280-1291 (1999).
23. Ashcroft, G.S. et al. Mice lacking Smad3 show accelerated wound healing and an impaired local inflammatory response. Nat. Cell Biol. 1, 260-266 (1999).
24. Tokumasa, A. et al. Reduction of Smad3 accelerates re-epithelialization in a murine model of colitis. Biochem. Biophys. Res. Commun. 317, 377-383 (2004).
25. Potts, J.D. & Runyan, R.B. Epithelial-mesenchymal cell transformation in the embryonic heart can be mediated, in part, by transforming growth factor beta. Dev. Biol. 134, 392-401 (1989).
26. Verheule, S. et al. Increased vulnerability to atrial fibrillation in transgenic mice with selective atrial fibrosis caused by overexpression of TGF-beta1. Circ. Res. 94, 1458-1465 (2004).
27. Hogan, B.L. Bone morphogenetic proteins in development. Curr. Opin. Genet. Dev. 6, 432-438 (1996).
28. Tarnavski, O. et al. Mouse cardiac surgery: comprehensive techniques for the generation of mouse models of human diseases and their application for genomic studies. Physiol. Genomics 16, 349-360 (2004).
29. Perrino, C. et al. Intermittent pressure overload triggers hypertrophy-independent cardiac dysfunction and vascular rarefaction. J. Clin. Invest. 116, 1547-1560 (2006).
30. Spindler, M. et al. Diastolic dysfunction and altered energetics in the alphaMHC403/+ mouse model of familial hypertrophic cardiomyopathy. J. Clin. Invest. 101, 1775-1783 (1998).
31. Sugimoto, H., Mundel, T.M., Kieran, M.W. & Kalluri, R. Identification of fibroblast heterogeneity in the tumor microenvironment. Cancer Biol. Ther. 5, 1640-1646 (2006).
32. Mandelbrot, D.A. et al. B7-dependent T-cell costimulation in mice lacking CD28 and CTLA4. J. Clin. Invest. 107, 881-887 (2001).
33. Lefer, A.M., Tsao, P.S., Ma, X.L. & Sampath, T.K. Anti-ischaemic and endothelial protective actions of recombinant human osteogenic protein (hOP-1). J. Mol. Cell. Cardiol. 24, 585-593 (1992).
34. Gould, S.E., Day, M., Jones, S.S. & Dorai, H. BMP-7 regulates chemokine, cytokine, and hemodynamic gene expression in proximal tubule cells. Kidney Int. 61, 51-60 (2002).
35. Nicoletti, A. & Michel, J.B. Cardiac fibrosis and inflammation: interaction with hemodynamic and hormonal factors. Cardiovasc. Res. 41, 532-543 (1999).
36. McMullen, J.R. et al. Phosphoinositide 3-kinase(p110alpha) plays a critical role for the induction of physiological, but not pathological, cardiac hypertrophy. Proc. Natl. Acad. Sci. USA 100, 12355-12360 (2003).
37. Villarreal, F.J. & Dillmann, W.H. Cardiac hypertrophy-induced changes in mRNA levels for TGF-beta 1, fibronectin, and collagen. Am. J. Physiol. 262, H1861-H1866 (1992).
38. Tomita, H. et al. Early induction of transforming growth factor-beta via angiotensin II type 1 receptors contributes to cardiac fibrosis induced by long-term blockade of nitric oxide synthesis in rats. Hypertension 32, 273-279 (1998).
39. Zeisberg, M. et al. Bone morphogenic protein-7 inhibits progression of chronic renal fibrosis associated with two genetic mouse models. Am. J. Physiol. Renal Physiol. 285, F1060-F1067 (2003).
40. Lips, D.J. et al. Left ventricular pressure-volume measurements in mice: comparison of closed-chest versus open-chest approach. Basic Res. Cardiol. 99, 351-359 (2004).
41. Sugimoto, H. et al. Bone-marrow-derived stem cells repair basement membrane collagen defects and reverse genetic kidney disease. Proc. Natl. Acad. Sci. USA 103, 7321-7326 (2006).
42. Lyden, D. et al. Impaired recruitment of bone-marrow-derived endothelial and hematopoietic precursor cells blocks tumor angiogenesis and growth. Nat. Med. 7, 1194-1201 (2001).
43. Takemoto, M. et al. Chronic angiotensin-converting enzyme inhibition and angiotensin II type 1 receptor blockade: effects on cardiovascular remodeling in rats induced by the long-term blockade of nitric oxide synthesis. Hypertension 30, 1621-1627 (1997).
44. Razeghi, P. et al. Lack of NF-kappaB1 (p105/p50) attenuates unloading-induced downregulation of PPARalpha and PPARalpha-regulated gene expression in rodent heart. Cardiovasc. Res. 74, 133-139 (2007).
45. Zeisberg, M. et al. BMP-7 counteracts TGF-beta1-induced epithelial-to-mesenchymal transition and reverses chronic renal injury. Nat. Med. 9, 964-968 (2003).
46. Zeisberg, E.M. et al. Morphogenesis of the right ventricle requires myocardial expression of Gata4. J. Clin. Invest. 115, 1522-1531 (2005).
47. Maeshima, Y. et al. Identification of the anti-angiogenic site within vascular basement membrane derived tumstatin. J. Biol. Chem. 7, 7 (2001).
48. Maresh, J.G., Xu, H., Jiang, N. & Shohet, R.V. In vivo transcriptional response of cardiac endothelium to lipopolysaccharide. Arterioscler. Thromb. Vasc. Biol. 24, 1836-1841 (2004).
49. Steidl, U. et al. Essential role of Jun family transcription factors in PU.1 knockdown-induced leukemic stem cells. Nat. Genet. 38, 1269-1277 (2006).
50. Okuno, Y. et al. Distal elements are critical for human CD34 expression in vivo. Blood 100, 4420-4426 (2002).