Resumen de Transforming growth factor-01 gene and protein expression associated with atherogenesis of cholesterol-fed rabbits
Y.-L. Chen, Helen W. Wu, M.J. Jlang
Transfonning growth factor-131 (TGF-131) has been shown to modulate both cell proliferation and the synthesis of extracellular matrix by vascular cells. This study was aimed to establish the temporal correlation between TGF-131 expression, the expression of the extracellular matrix protein fibronectin, and plaque development during atherogenesis of hypercholesterolemic rabbits. New Zealand White rabbits were fed with 2% cholesterol-supplemented chow for 1 week,2 weeks, 3 weeks or 6 weeks. TGF-131 mRNA and protein expression was examined in serial sections of aorta by in situ hybridization and immunohistochemistry. Fibronectin expression was examined by immunohistochemistry. In the control and I-week feeding group, the expression of TGF-Bl mRNA and protein was not apparent. In 2-week feeding group, intimal thickening was detected in which TGF-B 1 mRNA and protein were not clearly observed, either.
The 3-week and 6-week feeding groups exhibited fatty streaks in which TGF-Bl rnRNA and protein expression markedly increased as feeding proceeded. Cell typespecific staining indicated that TGF-131 was expressed by macrophages as well as smooth muscle cells of the fatty streaks. Immunostaining of fibronectin detected low expression levels in control, I-week and 2-week feeding groups with pronounced upregulation in the thickened intima and the proximal media in 3-week and 6-week feeding groups. These results implicate a role for TGF-Bl in modulating fatty streak formation and the synthesis of extracellular protein fibronectin during plaque development.
