The revised role of TGF-ß in aortic aneurysms in Marfan syndrome.
Neth Heart J
; 23(2): 116-21, 2015 Feb.
Article
em En
| MEDLINE
| ID: mdl-25342281
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-ß (TGF-ß) as therapeutic biomarker for effectiveness of losartan on AoDR.METHODS:
Baseline plasma TGF-ß levels of 22 healthy controls and 99 MFS patients, and TGF-ß 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-ß levels compared with healthy controls (121 pg/ml versus 54 pg/mL, p = 0.006). After 1 month of therapy, losartan normalised the TGF-ß level in 15 patients (36%); the other 27 patients (64%) showed a significant increase of TGF-ß. After 3 years of losartan therapy, patients with a decrease in TGF-ß had significantly higher AoDR compared with patients with increased TGF-ß (1.5 mm/3 years versus 0.5 mm/3 years, p = 0.04). Patients showing a decrease in TGF-ß after losartan therapy had significantly elevated baseline TGF-ß levels compared with patients with increased TGF-ß (189 pg/ml versus 94 pg/ml, p = 0.05).CONCLUSION:
Patients responding to losartan therapy with a reduction of the plasma TGF-ß level had higher baseline TGF-ß levels and a higher AoDR. Most likely, TGF-ß 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-ß levels in MFS. The concept of TGF-ß as initiator of aortic dilatation in MFS patients should be nuanced.
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MEDLINE
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article