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Our prior studies showed that in mice, EPFR inhalation impaired vascular relaxation in a dose- and endothelium-dependent manner. We also observed that activation of the aryl hydrocarbon receptor (AhR) in the alveolar type-II (AT-II) cells that form the air-blood interface stimulates the release of systemic factors that promote endothelial dysfunction in vessels peripheral to the lung. AhR is a recognized regulator of microRNA (miRNA) biogenesis, and miRNA control diverse signaling pathways. We thus hypothesized that systemic EPFR-induced vascular endothelial dysfunction is initiated via AhR activation in AT-II cells, resulting in a systemic release of miRNA. Using a combustion reactor, we generated EPFR of two free radical concentrations\u2014EPFR<jats:sub>lo<\/jats:sub> (10<jats:sup>16\u201317<\/jats:sup> radicals\/g particles) and EPFR (10<jats:sup>18\u201319<\/jats:sup> radicals\/g)\u2014and exposed mice by inhalation. EFPR inhalation resulted in changes in a distinct array of miRNA in the plasma, and these miRNAs are linked to multiple systemic effects, including cardiovascular diseases and dysregulation of cellular and molecular pathways associated with cardiovascular dysfunction. We identified 17 miRNA in plasma that were altered dependent upon both AhR activation in AT-II cells and\u2009~\u2009280\u00a0ug\/m<jats:sup>3<\/jats:sup> EPFR exposure. Using Ingenuity Pathway Analysis, we found that 5 of these miRNAs have roles in modulating endothelin-1 and endothelial nitric oxide signaling, known regulators of endothelial function. Furthermore, EPFR exposure reduced the expression of lung adherens and gap junction proteins in control mice but not AT-II-AhR deficient mice, and reductions in barrier function may facilitate miRNA release from the lungs. In summary, our findings support that miRNA may be systemic mediators promoting endothelial dysfunction mediated via EPFR-induced AhR activation at the air-blood interface.<\/jats:p>\n          <jats:p>\n            <jats:bold>Graphical Abstract<\/jats:bold>\n          <\/jats:p>","DOI":"10.1007\/s12012-025-09989-z","type":"journal-article","created":{"date-parts":[[2025,4,11]],"date-time":"2025-04-11T07:17:50Z","timestamp":1744355870000},"page":"651-665","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["AhR Activation at the Air-Blood Barrier Alters Systemic microRNA Release After Inhalation of Particulate Matter Containing Environmentally Persistent Free Radicals"],"prefix":"10.1007","volume":"25","author":[{"given":"Ankit","family":"Aryal","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashlyn C.","family":"Harmon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"No\u00ebl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingzhao","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kurt J.","family":"Varner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tammy R.","family":"Dugas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,4,11]]},"reference":[{"key":"9989_CR1","doi-asserted-by":"publisher","DOI":"10.1016\/j.scitotenv.2023.162163","volume":"872","author":"P Kumar","year":"2023","unstructured":"Kumar, P., Singh, A., Arora, T., Singh, S., & Singh, R. 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