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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 \u2018angiocentric molecules\u2019 may be promising biomarkers for COPD-PH.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Research Goal<\/jats:title>\n                    <jats:p>To identify angiocentric proteins elevated in individuals with suspected COPD-PH, defined by a pulmonary artery-to-aorta ratio (PA\/A)\u2009&gt;\u20091 on thoracic CT, and to evaluate if they are significantly associated with the severity of airflow limitation (FEV\u2081).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Study Design<\/jats:title>\n                    <jats:p>We analyzed plasma proteomic profiles from 1,056 COPDGene Phase-1 participants. Using PA\/A\u2009&gt;\u20091 as the outcome, we identified differentially abundant angiocentric proteins. We then assessed the abundance of angiocentric proteins in those with severe airflow obstruction (FEV\u2081 &lt;50% predicted) among both the COPDGene Phase-1 participants and 188 SPIROMICS Visit-1 participants, and validated the findings in an independent cohort of 363 COPDGene Phase-2 participants. Mediation analyses of multi-omic data examined the relationships between specific miR-126-3p and -p strands levels, their target mRNA and protein levels, and the severity of airflow obstruction.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Seventeen angiocentric proteins were increased in participants with PA\/A\u2009&gt;\u20091, with interleukin-1 receptor-like 1 (IL1RL1) and platelet-derived growth factor B (PDGFB) showing the most significant elevations. Among those with FEV\u2081 &lt;50% predicted, eleven angiocentric proteins were increased, including IL1RL1, angiopoietin-2, and peroxiredoxin-5. Mediation analyses supported a contribution of reduced miR-126 levels to lower FEV\u2081 via select angiocentric molecules, including the direct miR-126 target selenoprotein T. Additionally, LINC01506 and CAPZA1 had a mediation effect on multiple clinical outcomes, including FEV\u2081, DLCO, and hematocrit.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In addition to their role in pulmonary vascular remodeling, miR-126\u2013regulated angiocentric proteins are also linked to airflow limitation, highlighting their potential as candidate biomarkers for COPD-associated pulmonary hypertension.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12931-026-03622-5","type":"journal-article","created":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T05:07:17Z","timestamp":1774674437000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Vascular-related proteomic signatures in COPD with suspected pulmonary hypertension as predictors of FEV\u2081 impairment"],"prefix":"10.1186","volume":"27","author":[{"given":"Khushboo","family":"Goel","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryen","family":"Ormesher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine A.","family":"Pratte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koichi","family":"Nishino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig P.","family":"Hersh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katerina","family":"Kechris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Russell P.","family":"Bowler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina","family":"Petrache","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,28]]},"reference":[{"key":"3622_CR1","doi-asserted-by":"publisher","first-page":"1371","DOI":"10.1183\/09031936.00015608","volume":"32","author":"A Chaouat","year":"2008","unstructured":"Chaouat A, Naeije R, Weitzenblum E. 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