Role of Tgf-beta1 in Vascular Smooth Muscle Cell Apoptosis Induced by Angiotensin Ii.
From: Department of Pharmacology, School of Medicine, Universidad Complutense, Av. Complutense s/n, 28040 Madrid, Spain.
European journal of pharmacology
- Publish Date: Feb 2007
- ISSN: 0014-2999
- Volume: 556
- Issue: 1-3
- Pages: 36-44
- Medium: Print
- Language: English
- Citation (JAMA): Redondo Santiago, Ruiz Emilio, Padilla Eugenia, et al. Role of Tgf-beta1 in Vascular Smooth Muscle Cell Apoptosis Induced by Angiotensin Ii.. Eur. J. Pharmacol. Feb 2007;556:36-44
Abstract
Both Angiotensin II and transforming growth factor beta-1 (TGF-beta1) are important mediators of vascular smooth muscle cell function and have been reported to mediate the balance between proliferation and apoptosis. Some crosstalk between Angiotensin II and TGF-beta1 in end-organ hypertension has been established. However, whether TGF-beta1 is able to mediate Angiotensin II-induced vascular cell damage remains unknown. Vascular smooth muscle cells were obtained from rat thoracic aorta and cultured in 10% foetal calf serum. In all experiments, medium was changed to a low-serum (0.4% foetal calf serum) or serum-free one with or without Angiotensin II. Apoptosis was assessed by DNA fragmentation, DNA synthesis was measured as bromo-deoxyuridine uptake. TGF-beta1 production was determined by Enzyme-linked Immunosorbent Assay (ELISA) from cell conditioned media, RT-PCR from cell lysates and confocal immunostaining of fixed cells. Angiotensin II induced apoptosis in the absence of DNA synthesis when coincubated at 1 microM. Neither the specific anti-TGF-beta1 monoclonal antibody (50 microg/ml) nor the novel activin-like kinase (ALK)-4/5/7 synthetic inhibitor SB-431542 (4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide) at 10 microM were able to inhibit this effect. Angiotensin II induced expression of TGF-beta1 without further secretion of this cytokine. This effect was not affected by incubation with the AT1 inhibitor irbesartan (10 microM). A pharmacological approach to TGF-beta1 inhibition would be unable to reverse the apoptotic effect of Angiotensin II on vascular smooth muscle cells.
Mesh Headings (Keywords): Activin Receptors, Angiotensin II, Angiotensin II Type 1 Receptor Blockers, Animals, Apoptosis, Benzamides, Biphenyl Compounds, Cell Proliferation, Cells, Cultured, Dioxoles, Male, Muscle, Smooth, Vascular, Myocytes, Smooth Muscle, Rats, Rats, Inbred WKY, Tetrazoles, Transforming Growth Factor beta1
Check for Full Text / PubMed Unique Identifier (PMID): 17169354
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