Vascular Cell Responses to TGF-β3Mimic Those of TGF-β1in vitro

Abstract

The vascular cell responses to the type 3 isoform of transforming growth factor-beta (TGF-β₁ were studied using bovine aortic endothelial (BAECs) and smooth muscle cells (BASMCs) as well as rat epididymal fat pad microvascular endothelia (RFCs). Four distinct bioassays indicated that TGF-β₃ elicits results that do not differ significantly from those of the TGF-β₁ isoform in all three cell populations. Inhibition of proliferation by TGF-β₃ at a 5-day time point ranged from 85% on BAECs, to 55% and 53% on RFCs and BASMCs, respectively. The effects of TGF-β₃ and TGF-β₁ on cell migration were also found to be similar; migration of large vessel endothelial cells was inhibited 35%, while migration of smooth muscle cells was enhanced 30%. TGF-β₁ and TGF-β₃ also had equivalent effects on neovascularization while a 10-fold higher concentration of TGF-β₂ was required to elicit a similar response. Experimentation to decipher cell surface binding by the different isoforms revealed that iodinated TGF-β₁ bound to the surface of all three vascular cell types can be competed off in similar fashion by either TGF-β₁ or TGF-β₃; however, competition with TGF-β₂ produced unique binding profiles dependent upon the cell type examined. In summary, both the TGF-PI and TGF-β₃ isoforms of the transforming growth factor-beta family evoke comparable responses in proliferation, migration, angiogenic and cell surface binding assays using three distinct vascular cell types, while the biofunctions of TGF-β₂ on these cells are distinct.