Vascular-related proteomic signatures in COPD with suspected pulmonary hypertension as predictors of FEV₁ impairment

BACKGROUND: The development of pulmonary hypertension (PH) is a serious complication of chronic obstructive pulmonary disease (COPD). Despite advances in characterizing pulmonary vascular remodeling in COPD-PH, the lack of targeted therapies limits the routine use of gold-standard invasive diagnostics, highlighting the need for novel biomarkers. The pulmonary vascular endothelium is central to the pathogenesis of both PH and COPD. Since most endothelium-derived modulators of vascular tone and remodeling are targets of endothelial-enriched microRNA-126 (miR-126), a master vascular regulator that is suppressed in COPD, these and related ‘angiocentric molecules’ may be promising biomarkers for COPD-PH. RESEARCH GOAL: To identify angiocentric proteins elevated in individuals with suspected COPD-PH, defined by a pulmonary artery-to-aorta ratio (PA/A) > 1 on thoracic CT, and to evaluate if they are significantly associated with the severity of airflow limitation (FEV₁). STUDY DESIGN: We analyzed plasma proteomic profiles from 1,056 COPDGene Phase-1 participants. Using PA/A > 1 as the outcome, we identified differentially abundant angiocentric proteins. We then assessed the abundance of angiocentric proteins in those with severe airflow obstruction (FEV₁ 1, with interleukin-1 receptor-like 1 (IL1RL1) and platelet-derived growth factor B (PDGFB) showing the most significant elevations. Among those with FEV₁