Resumen de Efectos de un péptido derivado del receptor tipo iii del tgf-b1 o betaglicano sobre el desarrollo de la fibrosis miocárdica en un modelo experimental de hipertensión arterial
Aim: We investigated whether P144, a synthetic peptide from transforming growth factor-ß1 (TGF- ß1) type III receptor betaglycan, exhibits cardiac antifibrotic properties. Methods: The study was carried out in one group of 10-week-old normotensive Wistar-Kyoto rats treated with vehicle (WKY 22s), one group of 10-week-old spontaneously hypertensive rats treated with vehicle (SHR 22s), and one group of 10-week-old SHR treated with P144 (SHR P144) 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-ß1 were also studied.
Results: Compared with WKY 22s, SHR 22s exhibited significant increases in the myocardial expression of phosphorylated Smad2, 38 and 42 kDa connective tissue growth factor (CTGF) isoforms, procollagen α1 (I) mRNA and collagen type I protein, proteinase carboxi-terminal of procollagen type I (PCP) and its enhancer (PCPE) 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 SHR P144. TGF-ß1-stimulated fibroblasts exhibited significant increases in phosphorylated Smad2, 38 and 42 kDa CTGF proteins, and procollagen α1 (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.
Conclusions: These results show that P144 inhibits TGF-ß1-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.
