{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T15:54:55Z","timestamp":1753890895389,"version":"3.41.2"},"reference-count":21,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,12,8]],"date-time":"2021-12-08T00:00:00Z","timestamp":1638921600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cardiovasc. Med."],"abstract":"<jats:p><jats:bold>Objectives:<\/jats:bold> Interleukin-7 (IL-7) secures B cell maturation, regulatory T and natural killer (NK) cell survival, and homeostasis, all of which are important for beneficial immunomodulation in pulmonary arterial hypertension (PAH). However, the role and potential impact of IL-7, VEGF-C and the vascular injury markers ICAM-1, and VCAM-1 on the pathobiology and severity of PAH is unknown.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> EDTA blood was collected during cardiac catheterization from the superior vena cava (SVC), pulmonary artery (PA), and ascending aorta (AAO) in children with pulmonary hypertension (PH) [<jats:italic>n<\/jats:italic> = 10; 9.1 (3.9\u201318.5) years] and non-PH controls [<jats:italic>n<\/jats:italic> = 10; 10.5 (2.0\u201317.3) years]. Compartment-specific plasma concentrations of IL-7, VEGF-C, aldosterone, ICAM-1, and VCAM-1 were determined using Meso Scale Discovery's multi array technology and the LIAISON Aldosterone Assay.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> Children with PH had approximately 50% lower IL-7 (<jats:italic>p<\/jats:italic> &amp;lt; 0.01) and 59% lower VEGF-C plasma levels (<jats:italic>p<\/jats:italic> &amp;lt; 0.001) in the SVC, PA, and AAO versus non-PH controls. IL-7 and VEGF-C concentrations negatively correlated with the pulmonary vascular resistance (PVR)\/systemic vascular resistance (SVR) ratio (rho = \u22120.51 and <jats:italic>r<\/jats:italic> = \u22120.62, respectively). Central-venous IL-7 strongly positively correlated with VEGF-C (<jats:italic>r<\/jats:italic> = 0.81). Most patients had a step down in ICAM-1 and VCAM-1 plasma concentrations across the pulmonary circulation and both ICAM-1 and VCAM-1 transpulmonary gradients negatively correlated with invasive hemodynamics.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> This manuscript is the first report on decreased circulating IL-7 and VEGF-C plasma concentrations in human PAH and their inverse correlations with invasive surrogates of PAH severity. Additional and larger studies are needed to explore the role of the immune-modulatory IL-7 and VEGF-C in pediatric and adult PAH.<\/jats:p>","DOI":"10.3389\/fcvm.2021.794549","type":"journal-article","created":{"date-parts":[[2021,12,8]],"date-time":"2021-12-08T05:03:41Z","timestamp":1638939821000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Circulating Interleukin-7 in Human Pulmonary Arterial 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