{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T06:16:49Z","timestamp":1778221009506,"version":"3.51.4"},"reference-count":86,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T00:00:00Z","timestamp":1778198400000},"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. Cell Dev. Biol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Atherosclerosis (AS) remains a major cause of cardiovascular morbidity and mortality. Lactylation\u2014a recently described post-translational modification linking cellular metabolism to gene regulation\u2014has been implicated in vascular inflammation, yet its roles in AS are not fully defined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Method<\/jats:title>\n                    <jats:p>\n                      We modelled AS by exposing HUVECs to oxidised LDL and performed data-independent proteomics. Public AS transcriptomes were integrated and batch-corrected; lactylation-related genes (LRGs) were profiled; consensus clustering and WGCNA defined subtypes\/modules. Candidate biomarkers were prioritised by intersecting proteomic, differential and network features, then evaluated using an ensemble of 12 machine-learning algorithms with cross-validation and external validation. Immune infiltration (CIBERSORT) and single-cell data characterised immune contexts. Connectivity Map, molecular docking and molecular dynamics (MD) explored therapeutics. Core genes were validated by RT-qPCR, Western blotting and immunofluorescence in Apoe\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Proteomics identified 472 differentially expressed proteins; GEO analyses yielded 2,544 DEGs and WGCNA 2,059 module genes, converging on 25 candidates. The top ensemble (LASSO + GBM) achieved a mean AUC 0.979 across training and external sets, nominating UAP1, NRP1, QPRT and NDST1 as hub genes. These genes associated with immune-cell infiltration and showed prominent single-cell expression in macrophages and smooth muscle cells. RT-qPCR\n                      <jats:italic>in vivo<\/jats:italic>\n                      showed NRP1\/NDST1\/QPRT upregulated and UAP1 downregulated versus controls (all P &amp;lt; 0.05); WB\/IF confirmed higher NRP1 and lower UAP1 protein abundance. CMap analysis suggested several candidate compounds. Among them, rivaroxaban was prioritised for further\n                      <jats:italic>in silico<\/jats:italic>\n                      evaluation because NRP1 emerged as a validated hub gene, and docking and molecular dynamics simulations supported a stable predicted interaction between rivaroxaban and NRP1.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>UAP1, NRP1, QPRT and NDST1 represent lactylation-linked biomarkers of AS with diagnostic potential and plausible mechanistic relevance within immune-vascular pathways. Computational screening further prioritised a putative NRP1\u2013rivaroxaban interaction as a hypothesis-generating lead for future experimental validation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcell.2026.1742425","type":"journal-article","created":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T05:52:32Z","timestamp":1778219552000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Decoding atherosclerosis through lactylation: multi-omics integration with experimental validation"],"prefix":"10.3389","volume":"14","author":[{"given":"Yirong","family":"Ma","sequence":"first","affiliation":[{"name":"Department of Postgraduate, Jiangxi University of Chinese Medicine","place":["Nanchang, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiming","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Postgraduate, Jiangxi University of Chinese Medicine","place":["Nanchang, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Muge","family":"Wang","sequence":"additional","affiliation":[{"name":"Cardiology Department, Affiliated Hospital of Jiangxi University of Chinese Medicine","place":["Nanchang, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiang","family":"Wan","sequence":"additional","affiliation":[{"name":"Cardiology Department, Affiliated Hospital of Jiangxi University of Chinese Medicine","place":["Nanchang, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junyu","family":"Lai","sequence":"additional","affiliation":[{"name":"Cardiology Department, Affiliated Hospital of Jiangxi University of Chinese Medicine","place":["Nanchang, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianguang","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Postgraduate, Jiangxi University of Chinese Medicine","place":["Nanchang, China"]},{"name":"Cardiology Department, Affiliated Hospital of Jiangxi University of Chinese Medicine","place":["Nanchang, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuguang","family":"Wu","sequence":"additional","affiliation":[{"name":"Neurology Department, Jiangxi Province Hospital of Integrated Chinese and Western Medicine","place":["Nanchang, China"]},{"name":"Department of Postgraduate, Jiangxi University of Chinese Medicine","place":["Nanchang, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1007\/s11010-013-1831-3","article-title":"Vascular biomechanical properties in mice with smooth muscle specific deletion of Ndst1","volume":"385","author":"Adhikari","year":"2014","journal-title":"Mol. 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