Assessment of circulating biomarkers in patients with chronic thromboembolic pulmonary hypertension before and after surgical treatment
Year: 2026
Type: article
Study design: Observational Study
Abstract: Introduction. The role of aseptic inflammation and disturbances in the hemostasis and fibrinolysis systems has been demonstrated in the pathogenesis of chronic thromboembolic pulmonary hypertension (CTEPH); however, the profile and direction of changes in circulating markers vary significantly across studies, reflecting the complexity of the molecular mechanisms underlying CTEPH development. Aim: To assess the dynamics of circulating markers of inflammation, hemostasis, and endothelial dysfunction during surgical treatment of patients with CTEPH. Material and Methods. The study included 205 patients with a newly diagnosed case of CTEPH (median age 56.0 [44.0; 67.0] years; 47% male) selected for pulmonary thromboendarterectomy or balloon pulmonary angioplasty (BPA) between January 1, 2014, and January 1, 2024. All assessments were performed at two time points: at the time of diagnosis and 3–6 months after surgical treatment. We investigated plasma markers of inflammation (CRP, IL-6, IL-8, IL-10, IL-18, MCP-1, IP-10, MPO), fibrosis (MMP-9, MIG, galectin-3, osteopontin), endothelial dysfunction and growth factors (TGF-β, PDGF-B, VEGF, ET-1, sRAGE, HIF-1), as well as markers of hemostasis and fibrinolysis (vWF:Ag, FVIII, D-dimer, t-PA, TAFI, PAI-1). The control group included 30 healthy volunteers (mean age 50.3 [31.2; 63.4] years; 48% men). Results. Baseline elevations were observed in the levels of fibrinogen (p=0.002), vWF:Ag (p<0.001), FVIII (p<0.001), t-PA (p<0.001), CRP (p=0.032), and IL-8 (p=0.040), as well as in the concentrations of IP-10 (р<0.001) and MCP-1 (р=0.002), compared to the control group. Weak correlations were found between IP-10 and t-PA levels and markers of CTEPH severity. Increases in MPO (p<0.001), MMP-9 (p=0.017), sRAGE (p=0.035), osteopontin (p<0.001), and galectin-3 (p=0.001) levels were recorded compared to controls. Following surgical treatment, significant reductions in FVIII (p<0.001) and t-PA (p<0.001) levels were observed; the vWF:Ag level decreased but did not reach the value seen in the control group (p<0.01). A positive correlation was demonstrated between Δ t-PA and the magnitude of the reduction in CTEPH severity markers, such as PVR and the RV/LV ratio. A decrease was also observed in the levels of CRP (p<0.001), IL-10 (p=0.001), IP-10 (p<0.001), galectin-3 (p<0.001), and sRAGE (p=0.023), although these did not reach the levels seen in the control group. Levels of MCP-1 (p=0.002) and MPO (p<0.001) decreased over time to match those of the control group. MMP-9 levels did not decrease significantly following surgical treatment (p=0.236) and remained higher than those of the donors. Conclusion. Several markers associated with CTEPH have been identified, reflecting endothelial activation/dysfunction (vWF:Ag, t-PA, sRAGE) and inflammation (CRP, MCP-1, IP-10). Among the circulating markers analyzed, t-PA appears promising for further study as a predictor of the development of obstructive pulmonary vasculopathy. It has been shown that mechanical relief of pulmonary artery obstruction leads to a reduction in systemic inflammation and endothelial activation but does not result in complete normalization of the disease's biological phenotype within the first 3–6 months.
Institution: Federal Almazov North-West Medical Research Centre
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W7225113908