{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T19:24:27Z","timestamp":1793993067173,"version":"4.8.0"},"reference-count":215,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T00:00:00Z","timestamp":1776211200000},"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. Immunol."],"abstract":"<jats:p>Cardiovascular disease (CVD) remains the leading cause of mortality and disability worldwide, imposing a substantial burden on individuals, families, and healthcare systems. Despite major advances in controlling conventional risk factors (e.g., blood pressure, glycaemia, and lipids), a considerable residual risk persists, highlighting the need to elucidate additional pathogenic mechanisms and to develop more effective preventive and therapeutic strategies. Accumulating experimental and clinical evidence indicates that immune dysregulation and chronic low-grade inflammation are not merely associated with CVD but actively drive disease progression\u2014from lesion initiation to acute thrombotic events. These processes are further shaped by metabolic status, lifestyle factors, psychosocial stress, and environmental exposures, and age-related genetic immune changes such as clonal hematopoiesis of indeterminate potential (CHIP). Atherosclerosis, the predominant pathological substrate of most CVDs, is now widely recognized as a chronic immune-inflammatory disease. Emerging concepts including immunometabolic reprogramming, trained immunity(distinguished by central and peripheral subtypes), the thrombo-inflammatory axis, and allostatic load provide an integrative framework for understanding CVD as a systemic disorder. Here, we synthesize recent advances in innate and adaptive immune mechanisms, immunometabolic dysregulation, and inflammation\u2013thrombosis crosstalk that collectively govern plaque formation, destabilization, and clinical events. We also discuss how lifestyle-related factors (e.g., diet, fasting, physical activity, and stress) may modulate long-term cardiovascular risk through trained immunity and inflammatory pathways, and we highlight progress in immune biomarkers and anti-inflammatory interventions, and the immunometabolic effects of modern cardiometabolic drugs (GLP-1 receptor agonists, SGLT2 inhibitors). Additionally, we elaborate on the translational potential of short chain fatty acid derivatives in reversing innate immune inflammatory memory, and clarify the distinct cardiovascular toxic mechanisms of immune checkpoint inhibitors (ICIs) and chimeric antigen receptor T-cell (CAR-T) therapy in cardio-oncology. Conceptualizing CVD as a systemic immune\u2013metabolic\u2013inflammatory disease may facilitate improved risk stratification and inform precision prevention and treatment strategies.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1818835","type":"journal-article","created":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T04:43:55Z","timestamp":1776228235000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Immuno-inflammatory-metabolic interactions in cardiovascular diseases: a review from basic mechanisms to clinical translation"],"prefix":"10.3389","volume":"17","author":[{"given":"Xingshun","family":"Zhu","sequence":"first","affiliation":[{"name":"Department of Vascular and Endovascular Surgery, The First Affiliated Hospital of Yangtze University","place":["Jingzhou, China"]},{"name":"Department of Pharmacology, School of Medicine, Yangtze University","place":["Jingzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengmei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Vascular and Endovascular Surgery, The First Affiliated Hospital of Yangtze University","place":["Jingzhou, China"]},{"name":"Department of Pharmacology, School of Medicine, Yangtze University","place":["Jingzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxin","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Vascular and Endovascular Surgery, The First Affiliated Hospital of Yangtze University","place":["Jingzhou, China"]},{"name":"Department of Pharmacology, School of Medicine, Yangtze University","place":["Jingzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Vascular and Endovascular Surgery, The First Affiliated Hospital of Yangtze University","place":["Jingzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiawei","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Vascular and Endovascular Surgery, The First Affiliated Hospital of Yangtze University","place":["Jingzhou, China"]},{"name":"Department of Pharmacology, School of Medicine, Yangtze University","place":["Jingzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03392-8","article-title":"The changing landscape of atherosclerosis","volume":"592","author":"Libby","year":"2021","journal-title":"Nature"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1701719","article-title":"Clonal hematopoiesis and risk of atherosclerotic cardiovascular disease","volume":"377","author":"Jaiswal","year":"2017","journal-title":"N Engl J 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