Retinoids Inhibit the Actions of Angiotensin II on Vascular Smooth Muscle Cells

Haxsen, Volker; Adam-Stitah, Sylvie; Ritz, Eberhard; Wagner, Jürgen

doi:10.1161/01.res.88.6.637

Cited by 56 publications

(56 citation statements)

References 38 publications

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“…smooth muscle cells and renal tubular epithelial cells, indicate an activation of protein kinase C and p38 MAPK by ang II [11,26,27,28]. Furthermore, other reports have shown that ang II induces the DNA-binding activity of AP-1 proteins [29,30,31,32]. These observations suggest the possibility of an involvement of PKC, p38 MAPK and AP-1 in mediating non-haemodynamic effects of ang II.…”

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confidence: 76%

Angiotensin II induces human TGF-β1 promoter activation: similarity to hyperglycaemia

et al. 2002

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Aims/hypothesis. Activation of the renal renin-angiotensin system has been implicated in the pathogenesis of diabetic nephropathy. Because previous in vitro studies demonstrated the angiotensin II (ang II)-mediated up-regulation of the prosclerotic transforming growth factor β1 (TGF) we studied the molecular mechanism of ang II-induced TGF-β1 gene activation. Methods. Mesangial cells were stimulated with 100 nmol/l ang II with or without inhibitors of protein kinase C (PKC) and p38 MAPK and the TGF-β1 promoter activity was determined by promoter-reporter assays. The effect of ang II on the binding of nuclear proteins to the regulatory AP-1 site B, previously shown to mediate the high glucose-response of the TGF-β1 promoter, was studied by electrophoretic mobility shift assays. Results. Ang II enhanced the activity of the TGF-β1 promoter fragment -453/+11 approximately 1.6-fold.Mutation of each of two AP-1 binding sites or inhibition of the PKC-and p38 MAPK-dependent pathways blocked the ang II-stimulated activity completely. Furthermore, ang II activated the binding of nuclear proteins to the AP-1 box B of the TGF-β1 promoter. These effects were similar to those previously observed with high glucose. Co-incubation with ang II and high glucose had no additive effect on TGF-β1 promoter activity, protein binding to the AP-1 box B or activation of p38 MAPK. Conclusion/interpretation. The findings indicate that ang II and hyperglycaemia stimulate the TGF-β1 gene activation through the same PKC-and p38 MAPK-dependent pathways by the same regulatory elements of the TGF-β1 promoter. Our data could also be relevant for e.g. hypertension-induced glomerulosclerosis. [Diabetologia (2002) 45:890-898]

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confidence: 76%

Angiotensin II induces human TGF-β1 promoter activation: similarity to hyperglycaemia

et al. 2002

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“…8 In cultured aortic smooth muscle cells, ATRA induced apoptosis 9 and inhibited proliferation induced by serotonin, 10 platelet-derived growth factor, 11 endothelin-1, 12 and angiotensin II. 13 The suppression of smooth muscle cell proliferation by ATRA depends on retinoic acid receptors. 5,11,13,14 ATRA might also have potential for the prevention and/or treatment of pulmonary hypertension.…”

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confidence: 99%

“…13 The suppression of smooth muscle cell proliferation by ATRA depends on retinoic acid receptors. 5,11,13,14 ATRA might also have potential for the prevention and/or treatment of pulmonary hypertension. Indeed, ATRA feeding has been shown to inhibit pulmonary hypertension induced by monocrotaline in rats.…”

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confidence: 99%

Retinoids and Pulmonary Hypertension

et al. 2005

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Background-Retinoic acid has antimitogenic effects on smooth muscle cells. Studies on the systemic circulation suggest that it may reduce vascular thickening. Relationships between retinoids and pulmonary hypertension/pulmonary vascular remodeling, however, have not been explored. Thus, the present study examined retinoid levels in plasma of patients with idiopathic pulmonary arterial hypertension and the effects of retinoic acid on human pulmonary artery smooth muscle cell growth. Methods and Results-We measured retinoid levels by gas chromatograph-mass spectrometer technique in plasma of idiopathic pulmonary arterial hypertension patients and in age-and sex-matched healthy control subjects. Patients had significantly lower levels of all-trans retinoic acid and 13-cis retinoic acid than control subjects but similar 9-cis retinoic acid and retinol levels. In cultured human pulmonary artery smooth muscle cells, all-trans retinoic acid suppressed serotonin-induced cell growth. These cells were found to express the retinoid acid receptors RAR␣, RAR␤, RAR␥, RXR␣, and RXR␤. Gene array analysis showed that retinoic acid induces the expression of GADD45A, a known cell growth suppressor. Contrary to expectations, plasma from pulmonary hypertension patients suppressed cell growth, likely influenced by factors other than retinoids. Conclusions-Idiopathic

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“…Retinoids inhibit VSMC proliferation by modulating cell cycle regulators, such as by elevating p27 or inhibiting cyclin D, which results in the inhibition of retinoblastoma protein phosphorylation (22,23). Retinoids downregulate angiotensin II (AII) type 1 receptor expression in VSMCs, resulting in the inhibition of AII actions on VSMCs (24,25). Retinoids have also been reported to induce apoptosis in VSMCs (26,27).…”

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confidence: 99%