Connective Tissue Growth Factor and Cardiac Fibrosis after Myocardial Infarction

Rachael G Dean ^1*, Leanne C Balding ¹, Riccardo Candido ¹, Wendy C Burns ¹, Zemin Cao ¹, Stephen M Twigg ¹ and Louise M Burrell ¹

¹ Department of Medicine, University of Melbourne, Austin Health, Heidelberg, Victoria, Australia (RGD,LCB,RC,ZC,LMB); Diabetic Complications Group, Baker Heart Research Institue, Prahan, Victoria, Australia (WCB); and Kolling Institute of Medical Research, University of Sydney, Royal North Shore Hospital, St. Leonards, New South Wales, Australia (SMT)

^* To whom correspondence should be addressed. E-mail: rdean{at}unimelb.edu.au.

Submitted on October 25, 2005
Accepted on 11 May 2005

	Abstract

The temporal and spatial expression of transforming growth factor (TGF)-₁ and connective tissue growth factor (CTGF) was assessed in the left ventricle of a myocardial infarction (MI) model of injury with and without angiotensin converting enzyme (ACE) inhibition. Coronary artery ligated rats were killed 1, 3, 7, 28 and 180 days after MI. TGF-₁, CTGF and procollagen 1(I) mRNA were localized by in situ hybridization, and TGF-₁ and CTGF protein levels by immunohistochemistry. Collagen protein was measured using picrosirius red staining. In a separate group, rats were treated for 6 months with an ACE inhibitor. There were temporal and regional differences in the expression of TGF-₁, CTGF and collagen after MI. Procollagen 1(I) mRNA expression increased in the border zone and scar peaking one week after MI, while collagen protein increased in all areas of the heart over the 180 days. Expression of TGF-₁ mRNA and protein showed major increases in the border zone and scar peaking one week after MI. The major increases in CTGF mRNA and protein occurred in the viable myocardium at 180 days after MI. Long term ACE inhibition reduced LV mass and decreased fibrosis in the viable myocardium but had no effect on cardiac TGF-₁ or CTGF. TGF-₁ is involved in the initial, acute phase of inflammation and repair after MI, whereas CTGF is involved in the ongoing fibrosis of the heart. The anti-fibrotic benefits of captopril are not mediated through a reduction in CTGF.

Key Words: connective tissue growth factor, transforming growth factor ₁, myocardial infarction, fibrosis, angiotensin converting enzyme

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				A. J. Engler, C. Carag-Krieger, C. P. Johnson, M. Raab, H.-Y. Tang, D. W. Speicher, J. W. Sanger, J. M. Sanger, and D. E. Discher Embryonic cardiomyocytes beat best on a matrix with heart-like elasticity: scar-like rigidity inhibits beating J. Cell Sci., November 15, 2008; 121(22): 3794 - 3802. [Abstract] [Full Text] [PDF]

				L. Burchill, E. Velkoska, R. G. Dean, R. A. Lew, A. I. Smith, V. Levidiotis, and L. M. Burrell Acute kidney injury in the rat causes cardiac remodelling and increases angiotensin-converting enzyme 2 expression Exp Physiol, May 1, 2008; 93(5): 622 - 630. [Abstract] [Full Text] [PDF]

				B. Burstein, A. Maguy, R. Clement, H. Gosselin, F. Poulin, N. Ethier, J.-C. Tardif, T. E. Hebert, A. Calderone, and S. Nattel Effects of Resveratrol (trans-3,5,4'-Trihydroxystilbene) Treatment on Cardiac Remodeling following Myocardial Infarction J. Pharmacol. Exp. Ther., December 1, 2007; 323(3): 916 - 923. [Abstract] [Full Text] [PDF]

				M. Oka, S. Kubota, S. Kondo, T. Eguchi, C. Kuroda, K. Kawata, S. Minagi, and M. Takigawa Gene Expression and Distribution of Connective Tissue Growth Factor (CCN2/CTGF) During Secondary Ossification Center Formation J. Histochem. Cytochem., December 1, 2007; 55(12): 1245 - 1255. [Abstract] [Full Text] [PDF]

				J. L. Mehta and H. Attramadal The TGF{beta} superfamily in cardiovascular biology Cardiovasc Res, May 1, 2007; 74(2): 181 - 183. [Full Text] [PDF]

				M. Bujak and N. G. Frangogiannis The role of TGF-{beta} signaling in myocardial infarction and cardiac remodeling Cardiovasc Res, May 1, 2007; 74(2): 184 - 195. [Abstract] [Full Text] [PDF]

				N. de las Heras, M. Ruiz-Ortega, M. Ruperez, D. Sanz-Rosa, M. Miana, P. Aragoncillo, S. Mezzano, V. Lahera, J. Egido, and V. Cachofeiro Role of connective tissue growth factor in vascular and renal damage associated with hypertension in rats. Interactions with angiotensin II Journal of Renin-Angiotensin-Aldosterone System, December 1, 2006; 7(4): 192 - 200. [Abstract] [PDF]

				X.-J. Du, X.-M. Gao, H. Kiriazis, X.-L. Moore, Z. Ming, Y. Su, A. M. Finch, R. A. Hannan, A. M. Dart, and R. M. Graham Transgenic {alpha}1A-adrenergic activation limits post-infarct ventricular remodeling and dysfunction and improves survival Cardiovasc Res, September 1, 2006; 71(4): 735 - 743. [Abstract] [Full Text] [PDF]

				P. C.H. Hsieh, C. MacGillivray, J. Gannon;, F. U. Cruz, and R. T. Lee Local Controlled Intramyocardial Delivery of Platelet-Derived Growth Factor Improves Postinfarction Ventricular Function Without Pulmonary Toxicity Circulation, August 15, 2006; 114(7): 637 - 644. [Abstract] [Full Text] [PDF]

				Y.-M. Zhang, J. Bo, G. E. Taffet, J. Chang, J. Shi, A. K. Reddy, L. H. Michael, M. D. Schneider, M. L. Entman, R. J. Schwartz, et al. Targeted deletion of ROCK1 protects the heart against pressure overload by inhibiting reactive fibrosis FASEB J, May 1, 2006; 20(7): 916 - 925. [Abstract] [Full Text] [PDF]

				Q.-Y. Zhang, J.-B. Ge, J.-Z. Chen, J.-H. Zhu, L.-H. Zhang, C.-P. Lau, and H.-F. Tse Mast Cell Contributes to Cardiomyocyte Apoptosis after Coronary Microembolization J. Histochem. Cytochem., May 1, 2006; 54(5): 515 - 523. [Abstract] [Full Text] [PDF]

Guidelines | Subscriptions | About | exPRESS - Current - Archive | Business Information | Contact

The Journal of Histochemistry & Cytochemistry is owned, published, and licensed by The Histochemical Society © 2005