Cardiovascular Research Advance Access originally published online on November 19, 2008
Cardiovascular Research 2009 81(3):601-609; doi:10.1093/cvr/cvn315
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A synthetic peptide from transforming growth factor-β1 type III receptor prevents myocardial fibrosis in spontaneously hypertensive rats
1 Division of Cardiovascular Sciences, Centre for Applied Medical Research, University of Navarra, Pamplona, Spain
2 Division of Hepatology and Gene Therapy, Centre for Applied Medical Research, University of Navarra, Pamplona, Spain
3 Department of Cardiology and Cardiovascular Surgery, University Clinic, University of Navarra, Pamplona, Spain
* Corresponding author: Área de Ciencias Cardiovasculares, CIMA Avenida Pío XII 55, 31008 Pamplona, Spain. Tel: +34 948 194700; fax: +34 948 194716. E-mail address: jadimar{at}unav.es
Aim: We investigated whether P144, a synthetic peptide from transforming growth factor-β1 (TGF-β1) type III receptor betaglycan, exhibits cardiac antifibrotic properties.
Methods and results: The study was carried out in one group of 10-week-old normotensive Wistar-Kyoto rats treated with vehicle (V-WKY), one group of 10-week-old spontaneously hypertensive rats treated with vehicle (V-SHR), and one group of 10-week-old SHR treated with P144 (P144-SHR) for 12 weeks. Two more groups of 10-week-old untreated WKY and SHR were used to assess baseline values of the parameters tested. In addition, the effects of P144 on rat cardiac fibroblasts stimulated with TGF-β1 were also studied. Compared with V-WKY, V-SHR exhibited significant increases in the myocardial expression of phosphorylated Smad2, 38 and 42 kDa connective tissue growth factor (CTGF) isoforms, procollagen 
1 (I) mRNA, and collagen type I protein, as well as in the expression of lysyl oxidase (LOX) mRNA and protein, collagen cross-linking and deposition. P144 administration was associated with significant reduction in all these parameters in P144-SHR. TGF-β1-stimulated fibroblasts exhibited significant increases in phosphorylated Smad2, 38 and 42 kDa CTGF proteins, and procollagen 1 (I) mRNA compared with control fibroblasts. No significant differences were found in these parameters between fibroblasts incubated with TGF-β1 and P144 and control fibroblasts.
Conclusion: These results show that P144 inhibits TGF-β1-dependent signalling pathway and collagen type I synthesis in cardiac fibroblasts. These effects may be involved in the ability of this peptide to prevent myocardial fibrosis in SHR.
KEYWORDS Collagen; Hypertension; Myocardial fibrosis; Transforming growth factor-β1
Time for primary review: 31 days