title: 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).
  
  
  OBJECTIVE
  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.affiliation: Centre of Cardiology and Cardiovascular Surgery, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Mathias
authors.initials: M
authors.lastname: Hillebrand
authors.forename: Nathalie
authors.initials: N
authors.lastname: Millot
authors.forename: Sara
authors.initials: S
authors.lastname: Sheikhzadeh
authors.forename: Meike
authors.initials: M
authors.lastname: Rybczynski
authors.forename: Sabine
authors.initials: S
authors.lastname: Gerth
authors.forename: Tilo
authors.initials: T
authors.lastname: Kölbel
authors.forename: Britta
authors.initials: B
authors.lastname: Keyser
authors.forename: Kerstin
authors.initials: K
authors.lastname: Kutsche
authors.forename: Peter N
authors.initials: PN
authors.lastname: Robinson
authors.forename: Jürgen
authors.initials: J
authors.lastname: Berger
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Mir
authors.forename: Tanja
authors.initials: T
authors.lastname: Zeller
authors.forename: Stefan
authors.initials: S
authors.lastname: Blankenberg
authors.forename: Yskert
authors.initials: Y
authors.lastname: von Kodolitsch
authors.forename: Britta
authors.initials: B
authors.lastname: Goldmann
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D017545:Aortic Aneurysm, Thoracic / Q000097:blood* / Q000235:genetics; D001021:Aortic Valve / Q000002:abnormalities*; D000082882:Bicuspid Aortic Valve Disease; D005260:Female; D000071838:Fibrillin-1; D000071837:Fibrillins; D006349:Heart Valve Diseases / Q000097:blood* / Q000235:genetics; D006801:Humans; D055947:Loeys-Dietz Syndrome / Q000097:blood* / Q000235:genetics; D008297:Male; D008382:Marfan Syndrome / Q000097:blood* / Q000235:genetics; D008840:Microfilament Proteins / Q000235:genetics; D008875:Middle Aged; D009154:Mutation; D051881:Receptor, Notch1 / Q000235:genetics; D053773:Transforming Growth Factor beta1 / Q000097:blood*; D055815:Young Adult; D054392:Adipokines
chemical_list: D000071838:Fibrillin-1; D000071837:Fibrillins; D008840:Microfilament Proteins; D051881:Receptor, Notch1; D053773:Transforming Growth Factor beta1; C000605722:FBN1 protein, human; D054392:Adipokines; C497761:NOTCH1 protein, human; C508960:TGFB1 protein, human
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