Sato M, Ohsaki Y, Tobise K
First Department of Internal Medicine, Asahikawa Medical College, Japan.
Am J Hypertens. 1995 Feb;8(2):160-6. doi: 10.1016/0895-7061(94)00191-D.
To clarify whether the growth inhibitors, transforming growth factor-beta 1 (TGF-beta 1), heparin, and interferon-gamma (IFN-gamma) contribute to the development of vascular hypertrophy in spontaneously hypertensive rats (SHR), the growth of vascular smooth muscle cells (VSMC) was evaluated both for cell numbers over a period of 4 days, and [3H]thymidine incorporation over 24 h. Heparin and IFN-gamma inhibited the proliferation of VSMC from SHR and Wistar-Kyoto (WKY) rats. TGF-beta 1 enhanced SHR-VSMC proliferation by 16.6 +/- 8.9%; in contrast TGF-beta 1 inhibited WKY-VSMC proliferation by 60.5 +/- 7.4%. There was no difference in affinity, number of binding sites, or subtype expression of TGF-beta 1 receptor between SHR-VSMC and WKY-VSMC. This evidence suggests that the signal transduction system of TGF-beta 1 either the receptor itself or downstream signaling molecules, may be altered in SHR-VSMC versus WKY-VSMC. This abnormal responsiveness to TGF-beta 1 is involved in the proliferative characteristics of SHR-VSMC. Therefore, TGF-beta 1 could contribute to the development of hypertension or vascular hypertrophy in SHR.
为了阐明生长抑制剂、转化生长因子-β1（TGF-β1）、肝素和干扰素-γ（IFN-γ）是否促成自发性高血压大鼠（SHR）血管肥大的发展，对血管平滑肌细胞（VSMC）的生长进行了评估，包括4天内的细胞数量以及24小时内的[3H]胸腺嘧啶核苷掺入情况。肝素和IFN-γ抑制了SHR和Wistar-Kyoto（WKY）大鼠VSMC的增殖。TGF-β1使SHR-VSMC增殖增强了16.6±8.9%；相比之下，TGF-β1使WKY-VSMC增殖受到60.5±7.4%的抑制。SHR-VSMC和WKY-VSMC之间TGF-β1受体的亲和力、结合位点数量或亚型表达没有差异。这一证据表明，TGF-β1的信号转导系统，无论是受体本身还是下游信号分子，在SHR-VSMC与WKY-VSMC中可能发生了改变。这种对TGF-β1的异常反应性与SHR-VSMC的增殖特性有关。因此，TGF-β1可能促成SHR高血压或血管肥大的发展。
