Total serum transforming growth factor-β1 is elevated in the entire spectrum of genetic aortic syndromes.

Abstract

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.

• Authors: Mathias Hillebrand, Nathalie Millot, Sara Sheikhzadeh, Meike Rybczynski, Sabine Gerth, Tilo Kölbel, Britta Keyser, Kerstin Kutsche, Peter N Robinson, Jürgen Berger, Thomas S Mir, Tanja Zeller, Stefan Blankenberg, Yskert von Kodolitsch, Britta Goldmann
• Journal: Clinical cardiology (Clin Cardiol) Vol. 37 Issue 11 Pg. 672-9 (Nov 2014) ISSN: 1932-8737 [Electronic] United States
• PMID: 25113270 (Publication Type: Journal Article)
• Copyright: © 2014 Wiley Periodicals, Inc.

Chemical References

• FBN1 protein, human
• Fibrillin-1
• Fibrillins
• Microfilament Proteins
• NOTCH1 protein, human
• Receptor, Notch1
• TGFB1 protein, human
• Transforming Growth Factor beta1

Topics

• Adolescent
• Adult
• Aged
• Aortic Aneurysm, Thoracic (blood, genetics)
• Aortic Valve (abnormalities)
• Bicuspid Aortic Valve Disease
• Female
• Fibrillin-1
• Fibrillins
• Heart Valve Diseases (blood, genetics)
• Humans
• Loeys-Dietz Syndrome (blood, genetics)
• Male
• Marfan Syndrome (blood, genetics)
• Microfilament Proteins (genetics)
• Middle Aged
• Mutation
• Receptor, Notch1 (genetics)
• Transforming Growth Factor beta1 (blood)
• Young Adult