Collagen Triple Helix Repeat-Containing Protein 1 Is a Novel Biomarker of Right Ventricular Involvement in Pulmonary Hypertension

Pulmonary hypertension leads to right ventricular failure, which is a major determinant of prognosis. Circulating biomarkers for right ventricular function are poorly explored in pulmonary hypertension. This study aimed to clarify the significance of collagen triple helix repeat-containing protein 1 (CTHRC1) as a biomarker of right ventricular failure in pulmonary hypertension. A monocrotaline-induced pulmonary hypertension rat model was used to evaluate right ventricular CTHRC1 expression and its relationship with fibrosis. Next, human plasma CTHRC1 levels were measured in controls (n = 20), pulmonary arterial hypertension (n = 46), and patients with chronic thromboembolic pulmonary hypertension (CTEPH) (n = 64) before the first and after the final balloon pulmonary angioplasty. CTHRC1 expression was higher in the right ventricles of rats with monocrotaline-induced pulmonary hypertension than in those of controls. CTHRC1 was colocalized with vimentin and associated with fibrosis in the right ventricles. Plasma CTHRC1 levels were higher in human patients with pulmonary arterial hypertension (P = 0.006) and CTEPH (P = 0.011) than in controls. Plasma CTHRC levels were correlated with B-type natriuretic peptide (R = 0.355, P < 0.001), tricuspid lateral annular peak systolic velocity (R = –0.213, P = 0.029), and right ventricular fractional area change (R = –0.225, P = 0.017). Finally, plasma CTHRC1 levels were decreased after the final balloon pulmonary angioplasty (P < 0.001) in CTEPH. CTHRC1 can be a circulating biomarker associated with right ventricular function and fibrosis in pulmonary hypertension and might reflect the therapeutic efficacy of balloon pulmonary angioplasty in CTEPH. L’hypertension pulmonaire conduit à l’insuffisance ventriculaire droite, un déterminant majeur du pronostic. Les biomarqueurs circulants de la fonction ventriculaire droite n’ont pas été étudiés de manière approfondie en présence d’hypertension pulmonaire. Cette étude avait pour objectif de clarifier l’importance de la protéine CTHRC1 (collagen triple helix repeat containing 1) en tant que biomarqueur de l’insuffisance ventriculaire droite en présence d’hypertension pulmonaire. Nous avons utilisé un modèle d’hypertension pulmonaire induite par la monocrotaline chez le rat pour évaluer l’expression de la CTHRC1 dans le ventricule droit et sa relation avec la fibrose. Nous avons ensuite mesuré le taux de CTHRC1 dans le plasma humain chez des témoins (n = 20), chez des sujets a