Related Experiment Video
Updated: Apr 26, 2026
Visualization and Quantification of TGFβ/BMP/SMAD Signaling under Different Fluid Shear Stress Conditions using Proximity-Ligation-Assay
Published on: September 14, 2021
Total serum transforming growth factor-β1 is elevated in the entire spectrum of genetic aortic syndromes
Mathias Hillebrand1, Nathalie Millot, Sara Sheikhzadeh
1Centre of Cardiology and Cardiovascular Surgery, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.
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).
Hypothesis:
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.
Insights
Total serum transforming growth factor-beta 1 (tsTGF-β1) is elevated across genetic aortic syndromes, including Marfan syndrome (MFS) and bicuspid aortic valve disease (BAVD). These findings suggest tsTGF-β1 may serve as a biomarker for these conditions.
Area of Science:
- Cardiovascular Genetics
- Molecular Biology
- Biochemistry
Background:
- Total serum transforming growth factor-beta 1 (tsTGF-β1) is elevated in Marfan syndrome (MFS).
- tsTGF-β1 levels have not been previously assessed in thoracic aortic aneurysm and dissection (TAAD), Loeys-Dietz syndrome (LDS), and bicuspid aortic valve disease (BAVD).
Purpose of the Study:
- To investigate tsTGF-β1 levels in patients with TAAD, LDS, MFS, and BAVD.
- To determine if tsTGF-β1 is elevated across the spectrum of genetic aortic syndromes.
Main Methods:
- Measured tsTGF-β1 levels in 317 patients with suspected or known genetic aortic syndrome.
- Performed gene sequencing for FBN1, TGFBR1, and TGFBR2 mutations.
- Compared tsTGF-β1 levels between different genetic aortic syndromes and control groups.
Main Results:
- Elevated tsTGF-β1 levels were significantly associated with genetic aortic syndromes and causative gene mutations.
- tsTGF-β1 levels were elevated in MFS and BAVD compared to controls.
- Specific mutations, such as FBN1 and NOTCH1, showed increased tsTGF-β1 levels.
Conclusions:
- tsTGF-β1 is elevated in the full spectrum of genetic aortic syndromes.
- Gradual differences in tsTGF-β1 levels may reflect varying degrees of TGF-β1 pathway alteration in different genetic aortic syndromes.
Related Concept Videos
01:22Aortic Regurgitation II: Clinical Features and Diagnostic Tests
01:30Aneurysm I: Introduction
01:16TGF - β Signaling Pathway
01:15Aortic Regurgitation I: Introduction
01:21Aneurysm II: Clinical Manifestations and Diagnostic Studies
01:24Regulation of Angiogenesis and Blood Supply