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- aggregation classification "A1".
- aggregation creator B329701.
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- aggregation creator person.
- aggregation creator person.
- aggregation date "2009".
- aggregation format "application/pdf".
- aggregation hasFormat 856861.bibtex.
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- aggregation isPartOf urn:issn:0009-7322.
- aggregation language "eng".
- aggregation publisher "LIPPINCOTT WILLIAMS & WILKINS".
- aggregation title "Circulating Transforming Growth Factor-beta in Marfan Syndrome".
- aggregation abstract "Background-Marfan syndrome (MFS) is caused by mutations in the fibrillin-1 gene and dysregulation of transforming growth factor-beta (TGF-beta). Recent evidence suggests that losartan, an angiotensin II type 1 blocker that blunts TGF-beta activation, may be an effective treatment for MFS. We hypothesized that dysregulation of TGF-beta might be mirrored in circulating TGF-beta concentrations. Methods and Results-Serum obtained from MFS mutant mice (Fbn1(C1039G/+)) treated with losartan was analyzed for circulating TGF-beta 1 concentrations and compared with those from placebo-treated and wild-type mice. Aortic root size was measured by echocardiography. Data were validated in patients with MFS and healthy individuals. In mice, circulating total TGF-beta 1 concentrations increased with age and were elevated in older untreated Fbn1(C1039G/+) mice compared with wild-type mice (P = 0.01; n = 16; mean +/- SEM, 115 +/- 8 ng/mL versus n = 17; mean +/- SEM, 92 +/- 4 ng/mL). Losartan-treated Fbn1(C1039G/+) mice had lower total TGF-beta 1 concentrations compared with age-matched Fbn1(C1039G/+) mice treated with placebo (P = 0.01; n = 18; 90 +/- 5 ng/mL), and circulating total TGF-beta 1 levels were indistinguishable from those of age-matched wild-type mice (P = 0.8). Correlation was observed between circulating TGF-beta 1 levels and aortic root diameters in Fbn1(C1039G/+) and wild-type mice (P = 0.002). In humans, circulating total TGF-beta 1 concentrations were elevated in patients with MFS compared with control individuals (P < 0.0001; n = 53; 15 +/- 1.7 ng/mL versus n = 74; 2.5 +/- 0.4 ng/mL). MFS patients treated with losartan (n = 55) or beta-blocker (n = 80) showed significantly lower total TGF-beta 1 concentrations compared with untreated MFS patients (P <= 0.05). Conclusions-Circulating TGF-beta 1 concentrations are elevated in MFS and decrease after administration of losartan, beta-blocker therapy, or both and therefore might serve as a prognostic and therapeutic marker in MFS.".
- aggregation authorList BK621909.
- aggregation endPage "532".
- aggregation issue "6".
- aggregation startPage "526".
- aggregation volume "120".
- aggregation aggregates 912065.
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- aggregation similarTo CIRCULATIONAHA.108.841981.
- aggregation similarTo LU-856861.