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  • Title: A Possible Early Biomarker for Bicuspid Aortopathy: Circulating Transforming Growth Factor β-1 to Soluble Endoglin Ratio.
    Author: Forte A, Bancone C, Cobellis G, Buonocore M, Santarpino G, Fischlein TJM, Cipollaro M, De Feo M, Della Corte A.
    Journal: Circ Res; 2017 May 26; 120(11):1800-1811. PubMed ID: 28420669.
    Abstract:
    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.
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