Matt, Peter; Schoenhoff, Florian; Habashi, Jennifer; Holm, Tammy; Van Erp, Christel; Loch, David; Carlson, Olga D; Griswold, Benjamin F; Fu, Qin; De Backer, Julie; Loeys, Bart; Huso, David L; McDonnell, Nazli B; Van Eyk, Jennifer E; Dietz, Harry C (2009). Circulating transforming growth factor-beta in Marfan syndrome. Circulation, 120(6), pp. 526-32. Baltimore, Md.: Lippincott Williams & Wilkins 10.1161/CIRCULATIONAHA.108.841981
Full text not available from this repository.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-beta1 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-beta1 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-beta1 concentrations compared with age-matched Fbn1(C1039G/+) mice treated with placebo (P=0.01; n=18; 90+/-5 ng/mL), and circulating total TGF-beta1 levels were indistinguishable from those of age-matched wild-type mice (P=0.8). Correlation was observed between circulating TGF-beta1 levels and aortic root diameters in Fbn1(C1039G/+) and wild-type mice (P=0.002). In humans, circulating total TGF-beta1 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-beta1 concentrations compared with untreated MFS patients (P< or =0.05). CONCLUSIONS: Circulating TGF-beta1 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.
Item Type: |
Journal Article (Original Article) |
|---|---|
Division/Institute: |
04 Faculty of Medicine > Department of Cardiovascular Disorders (DHGE) > Clinic of Heart Surgery |
UniBE Contributor: |
Schönhoff, Florian |
ISSN: |
0009-7322 |
Publisher: |
Lippincott Williams & Wilkins |
Language: |
English |
Submitter: |
Factscience Import |
Date Deposited: |
04 Oct 2013 15:12 |
Last Modified: |
27 Feb 2024 14:29 |
Publisher DOI: |
10.1161/CIRCULATIONAHA.108.841981 |
PubMed ID: |
19635970 |
Web of Science ID: |
000268813300010 |
URI: |
https://boris.unibe.ch/id/eprint/31716 (FactScience: 196376) |
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