Biomarkers of collagen turnover and wound healing in chronic thromboembolic pulmonary hypertension patients before and after pulmonary endarterectomy

Background: In chronic thromboembolic pulmonary hypertension (CTEPH), fibrotic remodeling of tissue and thrombi contributes to disease progression. Removal of the thromboembolic mass by pulmonary endarterectomy (PEA) improves hemodynamics and right ventricular function, but the roles of different collagens before as well as after PEA are not well understood. Methods: In this study, hemodynamics and 15 different biomarkers of collagen turnover and wound healing were evaluated in 40 CTEPH patients at diagnosis (baseline) and 6 and 18 months after PEA. Baseline biomarker levels were compared with a historical cohort of 40 healthy subjects. Results: Biomarkers of collagen turnover and wound healing were increased in CTEPH patients compared with healthy controls, including a 35-fold increase in the PRO-C4 marker of type IV collagen formation and a 55-fold increase in the C3M marker of type III collagen degradation. PEA reduced pulmonary pressures to almost normal levels 6 months after the procedure, with no further improvement at 18 months. There were no changes in any of the measured biomarkers after PEA. Conclusions: Biomarkers of collagen formation and degradation are increased in CTEPH suggesting a high collagen turnover. While PEA effectively reduces pulmonary pressures, collagen turnover is not significantly modified by surgical PEA.