Transforming growth factor-beta 1 proliferated vascular smooth muscle cells from spontaneously hypertensive rats.
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.
Sato
M
M
First Department of Internal Medicine, Asahikawa Medical College, Japan.
Ohsaki
Y
Y
Tobise
K
K
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis / Q000187:drug effects; D006973:Hypertension / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D006984:Hypertrophy / Q000209:etiology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D004247:DNA