{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T05:14:03Z","timestamp":1783660443576,"version":"3.55.0"},"reference-count":20,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T00:00:00Z","timestamp":1782777600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Metabolic syndrome (MeS) is a major risk factor for cardiovascular disease and is characterized by chronic low-grade inflammation, immune dysregulation, and metabolic abnormalities. However, the molecular mechanisms linking MeS to diabetic coronary artery disease (DMCAD) remain incompletely understood. Publicly available peripheral blood mononuclear cell (PBMC) transcriptomic datasets of MeS and DMCAD were analyzed using an integrative bioinformatics approach. Differentially expressed genes (DEGs) were identified using the limma package, followed by functional enrichment, protein\u2013protein interaction (PPI) network construction, weighted gene co-expression network analysis (WGCNA), gene set enrichment analysis (GSEA), and miRNA regulatory network analysis. Candidate genes were further evaluated using an independent type 2 diabetes mellitus (T2DM) dataset for external transcriptomic validation. Integrated analyses identified immune-inflammatory and immuno-metabolic pathways as central features of both MeS and DMCAD. Enrichment analyses highlighted cytokine signaling, leukocyte activation, chemotaxis, complement activation, oxidative stress, and vascular inflammatory responses. Network analyses identified CD86, CD33, CCR1, C5AR1, FPR1, CXCL16, and LILRA5 as key hub genes associated with immune regulation and cardiometabolic dysfunction. External transcriptomic validation supported the relevance of CD33, CD86, and LILRA5. miRNA network analysis identified members of the miR-17\/92 family and miR-146a-5p as potential upstream regulators. TAM 2.0 enrichment analysis further linked these miRNAs to metabolic syndrome, diabetes mellitus, atherosclerosis, coronary heart disease, immune response, inflammation, and angiogenesis. Our findings suggest that coordinated immune-inflammatory and metabolic signaling networks contribute to the progression from MeS to DMCAD. The identified hub genes and miRNAs may serve as potential biomarkers and therapeutic targets for inflammation-driven cardiometabolic disease.<\/jats:p>","DOI":"10.3390\/ijms27135923","type":"journal-article","created":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:50:37Z","timestamp":1782867037000},"page":"5923","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Immuno-Metabolic Reprogramming in Metabolic Syndrome and Its Cardiovascular Complications: An Integrative Bioinformatics Study"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-9462-251X","authenticated-orcid":false,"given":"Komal","family":"Shrivastav","sequence":"first","affiliation":[{"name":"ICMR-National Institute for Tribal Health Research (NITHR), Jabalpur 482003, India"},{"name":"Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8966-7017","authenticated-orcid":false,"given":"Sushama","family":"Jadhav","sequence":"additional","affiliation":[{"name":"ICMR-National Institute of Translational Virology and AIDS Research (NITVAR), Pune 411026, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-3870-4488","authenticated-orcid":false,"given":"Pratik","family":"Mahajan","sequence":"additional","affiliation":[{"name":"Krishna Institute of Science and Technology, Krishna Vishwa Vidyapeeth (Deemed to be University), Karad 415539, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vijay","family":"Chauware","sequence":"additional","affiliation":[{"name":"ICMR-National Institute of Translational Virology and AIDS Research (NITVAR), Pune 411026, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6420-9397","authenticated-orcid":false,"given":"Vijay","family":"Nema","sequence":"additional","affiliation":[{"name":"ICMR-National Institute for Tribal Health Research (NITHR), Jabalpur 482003, India"},{"name":"Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Masenga, S.K., Kabwe, L.S., Chakulya, M., and Kirabo, A. 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