© 2000 by European Society of Cardiology
Copyright © 2000, European Society of Cardiology
Angiotensin II directly increases transforming growth factor β1 and osteopontin and indirectly affects collagen mRNA expression in the human heart
aInnere Medizin/Kardiologie, Virchow-Klinikum, Charité Humboldt University, and Deutsches Herzzentrum Berlin, Berlin, Germany
bHerz- Thorax- und Gefässchirurgie, Deutsches Herzzentrum Berlin, Berlin, Germany
* Corresponding author. Tel.: +49-30-4593-1000; fax: +49-30-4593-2500 zagrosek{at}dhzb.de
Objectives: Angiotensin II (Ang II) induces fibroblast proliferation and collagen synthesis in the myocardium, but its precise mechanisms of action in human hearts are still unknown. Therefore, we investigated whether Ang II directly affects the collagen mRNA content in the human myocardium and in isolated human cardiac fibroblasts or whether the growth factors TGFβ-1 and osteopontin are involved in this process. Methods and results I: In a first set of experiments, the direct effect of Ang II on collagen I, TGFβ-1 and osteopontin mRNA content in fresh samples of human atrial myocardium was determined by the use of a short stimulation period. After 4 h, Ang II-stimulated atrial samples gave a significantly higher expression of both TGFβ-1 (183±21% of control, p<0.05) and osteopontin mRNA (275±58%, p<0.02) than the controls. In contrast, the expression of collagen I mRNA was unchanged (95±8%). Stimulation with TGFβ-1 led to an increase in collagen I and III mRNA (127±10%, p<0.05; 140±15%, p<0.02). Methods and results II: In a second protocol, to assess the effects of longer stimulation periods, we determined the effects of Ang II and its potential mediator TGFβ-1 on collagen I, III and fibronectin mRNA expression and on proliferation of cultured human cardiac fibroblasts. Ang II caused a dose-dependent stimulation of proliferation but did not affect collagen I, III or fibronectin mRNA content after 24 h. In contrast, TGFβ-1 stimulation significantly increased collagen I and III mRNA expression (124±5% and 128±5%, p<0.002). Conclusions: In the human heart, Ang II does not directly increase collagen or fibronectin mRNA, but it does increase TGFβ-1 and osteopontin mRNA expression. Since TGFβ-1 induces collagen I and III mRNA in atrial samples and in isolated cardiac fibroblasts, it may represent a necessary mediator of the Ang II effects in the human heart.
KEYWORDS Ang II, Angiotensin II; AT1, AT2, angiotensin II receptor types 1 and 2; ADP, adenosine 5'-diphosphate; AMP, adenosine 5'-monophosphate; AP-1, activator protein 1; ATP, adenosine 5'-triphosphate; ATR, Ang II receptor; FN, fibronectin; HPLC, high-performance liquid chromatography; MAP, mitogen activated protein; mRNA, messenger RNA; OPN, osteopontin; PEA3, polyoma virus enhancer activator 3; PCR, polymerase chain reaction; PDH, pyruvic dehydrogenase; RT, reverse transcription; TGFβ-1, transforming growth factor β1
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  Y. K. On, E.-S. Jeon, S. Y. Lee, D.-H. Shin, J.-O. Choi, J. Sung, J. S. Kim, K. Sung, and P. Park Plasma transforming growth factor beta1 as a biochemical marker to predict the persistence of atrial fibrillation after the surgical maze procedure. J. Thorac. Cardiovasc. Surg., June 1, 2009; 137(6): 1515 - 1520. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. M. de Cavanagh, M. Ferder, F. Inserra, and L. Ferder Angiotensin II, mitochondria, cytoskeletal, and extracellular matrix connections: an integrating viewpoint Am J Physiol Heart Circ Physiol, March 1, 2009; 296(3): H550 - H558. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Burstein and S. Nattel Atrial Fibrosis: Mechanisms and Clinical Relevance in Atrial Fibrillation J. Am. Coll. Cardiol., February 26, 2008; 51(8): 802 - 809. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Leask TGF{beta}, cardiac fibroblasts, and the fibrotic response Cardiovasc Res, May 1, 2007; 74(2): 207 - 212. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Rutschow, J. Li, H.-P. Schultheiss, and M. Pauschinger Myocardial proteases and matrix remodeling in inflammatory heart disease Cardiovasc Res, February 15, 2006; 69(3): 646 - 656. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Groban, N. A. Pailes, C. D. L. Bennett, C. S. Carter, M. C. Chappell, D. W. Kitzman, and W. E. Sonntag Growth Hormone Replacement Attenuates Diastolic Dysfunction and Cardiac Angiotensin II Expression in Senescent Rats J. Gerontol. A Biol. Sci. Med. Sci., January 1, 2006; 61(1): 28 - 35. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Chen, J. L. Mehta, D. Li, L. Joseph, and J. Joseph Transforming Growth Factor {beta} Receptor Endoglin Is Expressed in Cardiac Fibroblasts and Modulates Profibrogenic Actions of Angiotensin II Circ. Res., December 10, 2004; 95(12): 1167 - 1173. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Zohar, B. Zhu, P. Liu, J. Sodek, and C. A. McCulloch Increased cell death in osteopontin-deficient cardiac fibroblasts occurs by a caspase-3-independent pathway Am J Physiol Heart Circ Physiol, October 1, 2004; 287(4): H1730 - H1739. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Rosenkranz TGF-{beta}1 and angiotensin networking in cardiac remodeling Cardiovasc Res, August 15, 2004; 63(3): 423 - 432. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. A. Walker, K. S. Masters, D. N. Shah, K. S. Anseth, and L. A. Leinwand Valvular Myofibroblast Activation by Transforming Growth Factor-{beta}: Implications for Pathological Extracellular Matrix Remodeling in Heart Valve Disease Circ. Res., August 6, 2004; 95(3): 253 - 260. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. F. Nadrous, J. H. Ryu, W. W. Douglas, P. A. Decker, and E. J. Olson Impact of Angiotensin-Converting Enzyme Inhibitors and Statins on Survival in Idiopathic Pulmonary Fibrosis Chest, August 1, 2004; 126(2): 438 - 446. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Hanna, S. Cardin, T.-K. Leung, and S. Nattel Differences in atrial versus ventricular remodeling in dogs with ventricular tachypacing-induced congestive heart failure Cardiovasc Res, August 1, 2004; 63(2): 236 - 244. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Sarkar, E. Vellaichamy, D. Young, and S. Sen Influence of cytokines and growth factors in ANG II-mediated collagen upregulation by fibroblasts in rats: role of myocytes Am J Physiol Heart Circ Physiol, July 1, 2004; 287(1): H107 - H117. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Diez Profibrotic Effects of Angiotensin II in the Heart: A Matter of Mediators Hypertension, June 1, 2004; 43(6): 1164 - 1165. [Full Text] [PDF]
|
|
|
|
|
|
T. Tsuruda, G. Boerrigter, B. K. Huntley, J. A. Noser, A. Cataliotti, L. C. Costello-Boerrigter, H. H. Chen, and J. C. Burnett Jr Brain Natriuretic Peptide Is Produced in Cardiac Fibroblasts and Induces Matrix Metalloproteinases Circ. Res., December 13, 2002; 91(12): 1127 - 1134. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Rocha, C. L. Martin-Berger, P. Yang, R. Scherrer, J. Delyani, and E. McMahon Selective Aldosterone Blockade Prevents Angiotensin II/Salt-Induced Vascular Inflammation in the Rat Heart Endocrinology, December 1, 2002; 143(12): 4828 - 4836. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Rodriguez-Pena, N. Eleno, A. Duwell, M. Arevalo, F. Perez-Barriocanal, O. Flores, N. Docherty, C. Bernabeu, M. Letarte, and J. M. Lopez-Novoa Endoglin Upregulation During Experimental Renal Interstitial Fibrosis in Mice Hypertension, November 1, 2002; 40(5): 713 - 720. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Mavroidis and Y. Capetanaki Extensive Induction of Important Mediators of Fibrosis and Dystrophic Calcification in Desmin-Deficient Cardiomyopathy Am. J. Pathol., March 1, 2002; 160(3): 943 - 952. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Bouzegrhane and G. Thibault Is angiotensin II a proliferative factor of cardiac fibroblasts? Cardiovasc Res, February 1, 2002; 53(2): 304 - 312. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Li, H. Chen, and J. L. Mehta Angiotensin II via Activation of Type 1 Receptor Upregulates Expression of Endoglin in Human Coronary Artery Endothelial Cells Hypertension, November 1, 2001; 38(5): 1062 - 1067. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. J Lijnen, V. V Petrov, and R. H Fagard Angiotensin II-induced stimulation of collagen secretion and production in cardiac fibroblasts is mediated via angiotensin II subtype 1 receptors Journal of Renin-Angiotensin-Aldosterone System, June 1, 2001; 2(2): 117 - 122. [Abstract] [PDF]
|
|
|
|
|
|
R. C. Tambascia, P. M. Fonseca, P. D. C. Corat, H. Moreno Jr, M. J. A. Saad, and K. G. Franchini Expression and Distribution of NOS1 and NOS3 in the Myocardium of Angiotensin II-Infused Rats Hypertension, June 1, 2001; 37(6): 1423 - 1428. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Fielitz, S. Hein, V. Mitrovic, R. Pregla, H. R. Zurbrugg, C. Warnecke, J. Schaper, E. Fleck, and V. Regitz-Zagrosek Activation of the cardiac renin-angiotensin system and increased myocardial collagen expression in human aortic valve disease J. Am. Coll. Cardiol., April 1, 2001; 37(5): 1443 - 1449. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. E. Dostal Regulation of Cardiac Collagen : Angiotensin and Cross-Talk With Local Growth Factors Hypertension, March 1, 2001; 37(3): 841 - 844. [Full Text] [PDF]
|
|