Circulating transforming growth factor-beta in Marfan syndrome

Area of Science:

• Genetics and Molecular Biology
• Cardiovascular Research
• Pharmacology

Background:

• Marfan syndrome (MFS) is a genetic disorder caused by fibrillin-1 gene mutations, leading to transforming growth factor-beta (TGF-beta) dysregulation.
• Emerging evidence suggests losartan, an angiotensin II type 1 receptor blocker, may effectively treat MFS by modulating TGF-beta activation.
• This study investigated whether TGF-beta dysregulation in MFS is reflected in circulating TGF-beta concentrations.

Purpose of the Study:

• To determine if circulating TGF-beta1 concentrations are elevated in Marfan syndrome.
• To assess the impact of losartan treatment on TGF-beta1 levels in MFS models and patients.
• To evaluate TGF-beta1 as a potential prognostic and therapeutic marker for MFS.

Main Methods:

• Analyzed serum TGF-beta1 concentrations in Marfan syndrome (MFS) mutant mice (Fbn1(C1039G/+)) treated with losartan versus placebo and wild-type controls.
• Measured aortic root size using echocardiography in mice.
• Validated findings in human patients with MFS and healthy individuals, comparing TGF-beta1 levels before and after treatment with losartan or beta-blockers.

Main Results:

• Circulating TGF-beta1 levels increased with age and were elevated in untreated MFS mice compared to wild-type.
• Losartan treatment significantly reduced TGF-beta1 concentrations in MFS mice to levels comparable to wild-type mice.
• Elevated TGF-beta1 levels were confirmed in human MFS patients, decreasing significantly after losartan or beta-blocker therapy.

Conclusions:

• Circulating TGF-beta1 concentrations are significantly elevated in Marfan syndrome.
• Losartan and beta-blocker therapies effectively reduce elevated TGF-beta1 levels in MFS.
• TGF-beta1 may serve as a valuable prognostic and therapeutic marker for Marfan syndrome management.