title: The revised role of TGF-β in aortic aneurysms in Marfan syndrome.
abstract: BACKGROUND
  Recently, we demonstrated that losartan reduced the aortic root dilatation rate (AoDR) in adults with Marfan syndrome (MFS); however, responsiveness was diverse. The aim was to determine the role of transforming growth factor-β (TGF-β) as therapeutic biomarker for effectiveness of losartan on AoDR.
  
  
  METHODS
  Baseline plasma TGF-β levels of 22 healthy controls and 99 MFS patients, and TGF-β levels after 1 month of losartan treatment in 42 MFS patients were measured. AoDR was assessed by magnetic resonance imaging at baseline and after 3 years of follow-up.
  
  
  RESULTS
  Patients with MFS had higher TGF-β levels compared with healthy controls (121 pg/ml versus 54 pg/mL, p = 0.006). After 1 month of therapy, losartan normalised the TGF-β level in 15 patients (36%); the other 27 patients (64%) showed a significant increase of TGF-β. After 3 years of losartan therapy, patients with a decrease in TGF-β had significantly higher AoDR compared with patients with increased TGF-β (1.5 mm/3 years versus 0.5 mm/3 years, p = 0.04). Patients showing a decrease in TGF-β after losartan therapy had significantly elevated baseline TGF-β levels compared with patients with increased TGF-β (189 pg/ml versus 94 pg/ml, p = 0.05).
  
  
  CONCLUSIONS
  Patients responding to losartan therapy with a reduction of the plasma TGF-β level had higher baseline TGF-β levels and a higher AoDR. Most likely, TGF-β levels may be considered to be a readout of the disease state of the aorta. We propose that increased angiotensin II is the initiator of aorta dilatation and is responsible for increased TGF-β levels in MFS. The concept of TGF-β as initiator of aortic dilatation in MFS patients should be nuanced.
authors.affiliation: Department of Cardiology, Academic Medical Centre Amsterdam, Amsterdam, the Netherlands.
authors.forename: R
authors.initials: R
authors.lastname: Franken
authors.forename: T
authors.initials: T
authors.lastname: Radonic
authors.forename: A W
authors.initials: AW
authors.lastname: den Hartog
authors.forename: M
authors.initials: M
authors.lastname: Groenink
authors.forename: G
authors.initials: G
authors.lastname: Pals
authors.forename: M
authors.initials: M
authors.lastname: van Eijk
authors.forename: R
authors.initials: R
authors.lastname: Lutter
authors.forename: B J M
authors.initials: BJ
authors.lastname: Mulder
authors.forename: A H
authors.initials: AH
authors.lastname: Zwinderman
authors.forename: V
authors.initials: V
authors.lastname: de Waard