Total serum transforming growth factor-?1 is elevated in the entire spectrum of genetic aortic syndromes.

ABSTRACT:

Background

Total serum transforming growth factor-beta 1 (tsTGF-?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-?1 is increased in genetic aortic syndromes including TAAD, LDS, MFS, and BAVD.

Methods

We measured tsTGF-?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?±?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-?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-?1 (P = 0.001). The tsTGF-?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-?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-?1 levels.

Conclusions

tsTGF-?1 is elevated in the entire spectrum of genetic aortic syndromes. However, gradual differences in the increases of tsTGF-?1 levels may mirror different degrees of alteration of tsTGF-?1 signaling in different genetic aortic syndromes.

SUBMITTER: Hillebrand M 

PROVIDER: S-EPMC6649456 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature