{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T05:04:55Z","timestamp":1784005495058,"version":"3.55.0"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T00:00:00Z","timestamp":1783987200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["nos. 82570425"],"award-info":[{"award-number":["nos. 82570425"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Vascular remodeling is a central pathological feature of cardiovascular diseases and is driven in part by vascular smooth muscle cell (VSMC) proliferation, migration, and phenotypic switching. The solute carrier family 7 member 5 (SLC7A5), a key amino acid transporter, has been implicated in cellular growth and metabolic regulation, but its role in vascular remodeling remains unclear. We investigated the contribution of SLC7A5 to VSMC activation and the underlying signaling mechanisms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods\/Results<\/jats:title>\n                    <jats:p>\n                      Differential expression analysis of the GSE220512 dataset revealed significant upregulation of Slc7a5 in mouse carotid arteries at Day 7 following wire injury compared with uninjured Day 0 controls (log\n                      <jats:sub>2<\/jats:sub>\n                      FC = 2.39, adjusted\n                      <jats:italic>P<\/jats:italic>\n                      = 0.0064). In a rat carotid artery balloon injury model, SLC7A5 expression was upregulated and localized to the medial layer.\n                      <jats:italic>In vitro<\/jats:italic>\n                      , platelet-derived growth factor-BB (PDGF-BB) increased SLC7A5 expression in VSMCs. Functional studies showed that siRNA-mediated knockdown of SLC7A5 attenuated PDGF-BB\u2013induced VSMC proliferation, migration, and phenotypic switching, as evidenced by reduced PCNA and MMP2 expression, decreased DNA synthesis, impaired migration, and partial restoration of \u03b1-smooth muscle actin expression. Mechanistically, SLC7A5 knockdown reduced phosphorylation of phosphatidylinositol 3-kinase (PI3K) and Akt without affecting total protein levels. Pharmacological inhibition of SLC7A5 using JPH203 produced similar effects\n                      <jats:italic>in vitro<\/jats:italic>\n                      and reduced neointimal hyperplasia and improved vascular function\n                      <jats:italic>in vivo<\/jats:italic>\n                      , with suppression of PI3K\/Akt signaling.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These findings identify SLC7A5 as a critical regulator of VSMC activation and vascular remodeling. SLC7A5 promotes proliferative and migratory responses, at least in part through activation of the PI3K\/Akt signaling pathway. Targeting SLC7A5 may represent a potential therapeutic strategy for vascular remodeling\u2013associated cardiovascular diseases.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1857850","type":"journal-article","created":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T04:22:00Z","timestamp":1784002920000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["SLC7A5 promotes vascular remodeling in the rat carotid artery following balloon injury through PI3K\/Akt signaling pathway"],"prefix":"10.3389","volume":"17","author":[{"given":"Yu","family":"Bai","sequence":"first","affiliation":[{"name":"Department of Cardiology, The First Affiliated Hospital of Harbin Medical University","place":["Harbin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sixuan","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Geriatrics, The First Affiliated Hospital of Harbin Medical University","place":["Harbin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The First Affiliated Hospital of Harbin Medical University","place":["Harbin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiming","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The First Affiliated Hospital of Harbin Medical University","place":["Harbin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dechun","family":"Yin","sequence":"additional","affiliation":[{"name":"Department of Geriatrics, The First Affiliated Hospital of Harbin Medical University","place":["Harbin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,14]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1038\/s41588-020-00753-3","article-title":"The amino acid transporter SLC7A5 is required for efficient growth of KRAS-Mutant colorectal cancer","volume":"53","author":"Arafath","year":"2021","journal-title":"J. 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