The revised role of TGF-β in aortic aneurysms in Marfan syndrome

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-beta (TGF-beta) as therapeutic biomarker for effectiveness of losartan on AoDR. Methods Baseline plasma TGF-beta levels of 22 healthy controls and 99 MFS patients, and TGF-beta 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-beta levels compared with healthy controls (121 pg/ml versus 54 pg/mL, p=0.006). After 1 month of therapy, losartan normalised the TGF-beta level in 15 patients (36%); the other 27 patients (64%) showed a significant increase of TGF-beta. After 3 years of losartan therapy, patients with a decrease in TGF-beta had significantly higher AoDR compared with patients with increased TGF-beta (1.5 mm/3 years versus 0.5 mm/3 years, p=0.04). Patients showing a decrease in TGF-beta after losartan therapy had significantly elevated baseline TGF-beta levels compared with patients with increased TGF-beta (189 pg/ml versus 94 pg/ml, p=0.05). Conclusion Patients responding to losartan therapy with a reduction of the plasma TGF-beta level had higher baseline TGF-beta levels and a higher AoDR. Most likely, TGF-beta 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-beta levels in MFS. The concept of TGF-beta as initiator of aortic dilatation in MFS patients should be nuanced.