{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T06:52:58Z","timestamp":1791355978993,"version":"4.3.1"},"reference-count":41,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"19","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2026,10,6]]},"abstract":"<jats:sec xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">Previous research has highlighted aerobic exercise as beneficial for patients with pulmonary hypertension (PH) and it is often recommended as a key therapeutic approach. However, the specific mechanisms behind these benefits are not yet fully understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p xml:lang=\"en\">A murine model of hypoxia\u2010induced PH was developed, and the mice underwent 4\u2009weeks of exercise training. The underlying mechanisms were elucidated by utilizing transcriptomic sequencing, in\u00a0situ immunofluorescence, flow cytometry, cell culture, in\u00a0vivo mouse experiments, and clinical cohort.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p xml:lang=\"en\">Aerobic exercise effectively improved hypoxia\u2010induced pulmonary vascular and right ventricular remodeling. Transcriptomic profiling revealed a marked suppression of inflammatory pathways, with S100A9 identified as the most significantly regulated factor. Under physiological conditions, S100A9 expression is minimal and largely restricted to lung neutrophils; however, hypoxia induces its robust upregulation and widespread distribution, while remaining predominantly neutrophil\u2010associated. Elevated S100A9 promoted immune cell recruitment and impaired pulmonary artery smooth muscle cell function via activation of the TLR4\u2010MyD88\u2010ERK signaling pathway, whereas pharmacological inhibition of S100A9 reduced immune infiltration and restored pulmonary artery smooth muscle cell function. Furthermore, increased S100A9 expression was validated in pulmonary fibrosis\u2013induced PH and in patients with chronic obstructive pulmonary disease associated with PH. The benefits of aerobic exercise in chronic obstructive pulmonary disease associated with PH may be mediated by S100A9 downregulation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">These findings suggest that aerobic exercise alleviates PH by suppressing S100A9\u2010mediated inflammation and vascular remodeling, identifying S100A9 as a biomarker and therapeutic target, and supporting combined exercise rehabilitation and S100A9\u2010targeted therapy for group 3 PH.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/jaha.125.049578","type":"journal-article","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T11:14:21Z","timestamp":1790680461000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["S100A9 Inhibition Mediates Aerobic Exercise Benefits in Pulmonary 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