Total Serum Transforming Growth Factor-β1 Is Elevated in the Entire Spectrum of Genetic Aortic Syndromes
| Autor: | Nathalie Millot, Sabine Gerth, Meike Rybczynski, Sara Sheikhzadeh, Britta Keyser, Stefan Blankenberg, Tilo Kölbel, Mathias Hillebrand, Britta U. Goldmann, Jürgen Berger, Kerstin Kutsche, Tanja Zeller, Thomas S. Mir, Peter N. Robinson, Yskert von Kodolitsch |
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| Rok vydání: | 2014 |
| Předmět: |
Marfan syndrome
Aortic valve Mutation Pathology medicine.medical_specialty biology business.industry General Medicine medicine.disease_cause medicine.disease Loeys–Dietz syndrome Gastroenterology Thoracic aortic aneurysm Aortic aneurysm medicine.anatomical_structure Bicuspid aortic valve Internal medicine cardiovascular system medicine biology.protein ACTA2 Cardiology and Cardiovascular Medicine business |
| Zdroj: | Clinical Cardiology. 37:672-679 |
| ISSN: | 0160-9289 |
| Popis: | Background Total serum transforming growth factor-beta 1 (tsTGF-β1) is increased in patients with Marfan syndrome (MFS), but it has not been assessed in thoracic aortic aneurysm and dissection (TAAD), Loeys-Dietz syndrome (LDS), and bicuspid aortic valve disease (BAVD). Hypothesis tsTGF-β1 is increased in genetic aortic syndromes including TAAD, LDS, MFS, and BAVD. Methods We measured tsTGF-β1 and performed sequencing of the genes FBN1, TGFBR1, and TGFBR2 in 317 consecutive patients with suspected or known genetic aortic syndrome (167 men, 150 women; mean age 43 ± 14 years). TAAD was diagnosed in 20, LDS in 20, MFS in 128, and BAVD in 30 patients, and genetic aortic syndrome was excluded in 119 patients. Results Elevated tsTGF-β1 levels were associated with causative gene mutations (P = 0.008), genetic aortic syndrome (P = 0.009), and sporadic occurrence of genetic aortic syndrome (P = 0.048), whereas only genetic aortic syndrome qualified as an independent predictor of tsTGF-β1 (P = 0.001). The tsTGF-β1 levels were elevated in FBN1 and NOTCH1 mutations vs patients without mutations (both P = 0.004), and in NOTCH1 mutations vs ACTA2/MYH11 mutations (P = 0.015). Similarly, tsTGF-β1 levels were elevated in MFS (P = 0.003) and in BAVD (P = 0.006) vs patients without genetic aortic syndrome. In contrast to specific clinical features of MFS, FBN1 in-frame mutations (P = 0.019) were associated with increased tsTGF-β1 levels. Conclusions tsTGF-β1 is elevated in the entire spectrum of genetic aortic syndromes. However, gradual differences in the increases of tsTGF-β1 levels may mirror different degrees of alteration of tsTGF-β1 signaling in different genetic aortic syndromes. |
| Databáze: | OpenAIRE |
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