Abstract
Background/Objectives: Angiogenesis is involved in the pathogenesis of hereditary hemorrhagic telangiectasia (HHT). VEGF, ANG2, TGFβ1, and ENG are the most studied angiogenic factors, but their clinical significance in blood samples is still not completely defined. The genetic study of HHT mutations is the test of choice for diagnosing the disease, but this route is expensive, and the causative mutation is not found in up to 10% of cases. Therefore, the use of angiogenic biomarkers could facilitate a cheaper and easier approach to the diagnosis of HHT. To determine the diagnostic and prognostic value of the VEGFA, TGFβ1, ANG2, and ENG plasmatic concentrations in patients with HHT. Methods: All the participants were clinically evaluated and the concentrations of these angiogenic factors were measured using MILLIPLEX(®)MAP immunoassays in plasma samples collected from 44 patients with HHT and 19 controls. To evaluate the diagnostic validity of these parameters, we estimated the maximum Youden index of the ROC curve and evaluated their diagnostic value using multiple logistic regression. Results: Patients with HHT had increased blood levels of TGFβ1 and decreased ENG compared to the control group. We could not identify any angiogenic markers related to the clinical severity or epistaxis. TGFβ1 and ENG exhibited a higher discriminant capacity for HHT, especially patients with HHT1, and it was possible to develop signatures of these factors with diagnostic value. Conclusions: We identified several angiogenic factors that may be important diagnostic biomarkers for HHT and propose that the combination of TGFβ1 and ENG could represent a signature with diagnostic value for this disease.