Related Experiment Video
Updated: Mar 4, 2026
Coronary Progenitor Cells and Soluble Biomarkers in Cardiovascular Prognosis after Coronary Angioplasty
Published on: January 28, 2020
A Possible Early Biomarker for Bicuspid Aortopathy: Circulating Transforming Growth Factor β-1 to Soluble Endoglin
Amalia Forte1, Ciro Bancone2, Gilda Cobellis2
1From the Experimental Medicine (A.F., M.C.), Cardiothoracic Sciences (C.B., M.B., M.D.F., A.D.C.), and Biophysics, Biochemistry, and General Pathology (G.C.), University of Campania "L.Vanvitelli", Naples Italy; and Department of Cardiac Surgery, Cardiovascular Center, Paracelsus Medical University, Nürnberg, Germany (G.S., T.J.M.F.). amalia.forte@unina2.it aledellacorte@libero.it.
Rationale:
The pathogenesis of bicuspid aortic valve (BAV)-associated aortopathy is poorly understood, and no prognostic biomarker is currently available.
Objective:
We aimed to identify putative circulating biomarkers pathogenetically and prognostically linked to bicuspid aortopathy.
Methods And Results:
By reverse transcription polymerase chain reaction, we evaluated gene expression variations (versus normal aorta) of transforming growth factor-β1 (TGF-β1), connective tissue growth factor, matrix metalloproteinase-2 (MMP-2), MMP-14, endoglin (ENG), and superoxide dismutase 3 in ascending aorta samples from 50 tricuspid and 70 patients with BAV undergoing surgery for aortic stenosis (aorta diameter ≤45 mm: BAVnon-dil or >45 mm: BAVdil). Expression changes of the TGF-β1 active dimer and ENG were analyzed also by Western blot in ascending aorta samples from other 10 tricuspid aortic valve, 10 BAVnon-dil, and 10 BAVdil patients. The serum concentration of study targets was assessed through ELISA and the ratio of serum TGF-β1/ENG (T/E) was evaluated. All BAVnon-dil patients underwent follow-up echocardiography to assess aortic growth rate. In BAVnon-dil patients, TGF-β1 and MMP-2 gene expression increased significantly, whereas MMP-14 and ENG expression decreased versus controls. Expression changes were confirmed at protein level for TGF-β1 and ENG. TGF-β1 serum concentration significantly decreased in tricuspid aortic valve and BAVnon-dil patients versus healthy subjects. ENG serum concentration decreased in all patients, more markedly in BAVdil. A significant increase of the T/E ratio versus healthy subjects was unique of patients with BAV. In BAVnon-dil patients, a T/E ≥9 was independently associated in multivariable analysis with higher MMP-2 and lower superoxide dismutase 3 gene expression, independent of age and aortic diameter. A significant correlation was observed between baseline T/E ratio and aortic diameter growth rate in BAVnon-dil patients (r=0.66, P<0.001).
Conclusions:
The novel evidence of a possible value of the T/E ratio as a biomarker of BAV aortopathy was presented: further validation studies are warranted.
