{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T18:33:18Z","timestamp":1791657198367,"version":"4.3.4"},"reference-count":48,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T00:00:00Z","timestamp":1779235200000},"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. Physiol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Atherosclerosis (AS) is a chronic inflammatory disease and a leading cause of global morbidity and mortality. Dysregulated expression of the long non-coding RNA (lncRNA) H19 has been implicated in AS progression. However, the underlying molecular mechanisms remain unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      To determine the role of H19 in AS, the AS mouse model was established using ApoE\n                      <jats:sup>-\/-<\/jats:sup>\n                      mice fed a high-fat diet, and the AS cell model was generated by stimulating human umbilical vein endothelial cells (HUVECs) with oxidized low-density lipoprotein (oxLDL). H19 expression levels were subsequently measured. To investigate the underlying mechanism, H19 siRNA and was transfected into cells, and adeno-associated virus (AAV) expressing short hairpin RNA targeting H19 (AAV-sh-H19) was administered to mice to evaluate the functional impact of H19 on AS.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Result<\/jats:title>\n                    <jats:p>H19 was markedly upregulated in the aortae of AS mice and in the AS cell model, which correlated with enhanced adhesion molecule expression and systemic cytokine release. Mechanistically, H19 functioned as a molecular sponge for microRNA let-7a (miR-let-7a), thereby relieving the repression of its target integrin subunit beta 3 (ITGB3) and amplifying VCAM-1\/ICAM-1\/N-cadherin-dependent leukocyte recruitment. Luciferase reporter assays confirmed that miR-let-7a is a direct target of H19. Moreover, H19 knockdown increased miR-let-7a levels, thereby inhibiting endothelial cell adhesion and inflammatory responses. Conversely, treatment of mice with AAV-sh-H19 markedly attenuated AS lesion formation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These findings indicate that the H19\/miR-let-7a\/ITGB3 axis constitutes a targetable inflammatory checkpoint that links endothelial dysfunction to plaque initiation, highlighting H19 inhibition as a potential therapeutic target.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphys.2026.1801950","type":"journal-article","created":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T04:48:42Z","timestamp":1779252522000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["LncRNA H19 drives atherosclerosis progression via the miR-let-7a\/ITGB3 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