Total Serum Transforming Growth Factor-[beta]1 Is Elevated in the Entire Spectrum of Genetic Aortic Syndromes
Background Total serum transforming growth factor-beta 1 (tsTGF-[beta]1) 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-[beta]1...
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Published in | Clinical cardiology (Mahwah, N.J.) Vol. 37; no. 11; p. 672 |
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Main Authors | , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Hoboken
John Wiley & Sons, Inc
01.11.2014
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Online Access | Get full text |
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Summary: | Background Total serum transforming growth factor-beta 1 (tsTGF-[beta]1) 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-[beta]1 is increased in genetic aortic syndromes including TAAD, LDS, MFS, and BAVD. Methods We measured tsTGF-[beta]1 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±14years). 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-[beta]1 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-[beta]1 (P = 0.001). The tsTGF-[beta]1 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-[beta]1 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-[beta]1 levels. Conclusions tsTGF-[beta]1 is elevated in the entire spectrum of genetic aortic syndromes. However, gradual differences in the increases of tsTGF-[beta]1 levels may mirror different degrees of alteration of tsTGF-[beta]1 signaling in different genetic aortic syndromes. |
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ISSN: | 0160-9289 1932-8737 |
DOI: | 10.1002/clc.22320 |