Transforming growth factor-ß1 gene and protein expression associated with atherogenesis of cholesterol-fed rabbits

Y.-L. Chen1, H.-W. Wu1 and M.J. Jiang2

1Institute of Anatomy, National Yang-Ming University, Shih-Pai, Taipei and 2Department of Anatomy, National Cheng Kung University Medical College, Tainan, Taiwan

Offprint requests to: Meei Jyh Jiang, National Cheng Kung University Medical College, Department of Anatomy, Tainan 70101, Taiwan. e-mail: mjiang@mail.ncku.edu.tw

Summary. Transforming growth factor-ß1 (TGF-ß1) 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-ß1 expression, the expression of the extracellular matrix protein fibronectin, and plaque development during atherogenesis of hyper-cholesterolemic rabbits. New Zealand White rabbits were fed with 2% cholesterol-supplemented chow for 1 week, 2 weeks, 3 weeks or 6 weeks. TGF-ß1 mRNA and protein expression was examined in serial sections of aorta by in situ hybridization and immunohisto-chemistry. Fibronectin expression was examined by immunohistochemistry. In the control and 1-week feeding group, the expression of TGF-ß1 mRNA and protein was not apparent. In 2-week feeding group, intimal thickening was detected in which TGF-ß1 mRNA and protein were not clearly observed, either. The 3-week and 6-week feeding groups exhibited fatty streaks in which TGF-ß1 mRNA and protein expression markedly increased as feeding proceeded. Cell type-specific staining indicated that TGF-ß1 was expressed by macrophages as well as smooth muscle cells of the fatty streaks. Immunostaining of fibronectin detected low expression levels in control, 1-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-ß1 in modulating fatty streak formation and the synthesis of extracellular protein fibronectin during plaque development. Histol. Histopathol. 15, 421-428 (2000)

Key words: Transforming growth factor-ß1, Athero-genesis, Fibronectin, In situ hybridization, Immunohistochemistry

DOI: 10.14670/HH-15.421