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It was believed for a long time that memory formation exclusively occurs in the adaptive part of the immune system with the formation of highly specific memory T cells and B cells. In the past 10\u201315 years, it has become clear that innate immune cells, such as monocytes, natural killer cells, or neutrophil granulocytes, also have the ability to generate some kind of memory. After the exposure of innate immune cells to certain stimuli, these cells develop an enhanced secondary response with increased cytokine secretion even after an encounter with an unrelated stimulus. This phenomenon has been termed trained innate immunity (TI) and is associated with epigenetic modifications (histone methylation, acetylation) and metabolic alterations (elevated glycolysis, lactate production). TI has been observed in tissue-resident or circulating immune cells but also in bone marrow progenitors. Risk-factors for cardiovascular diseases (CVDs) which are associated with low-grade inflammation, such as hyperglycemia, obesity, or high salt, can also induce TI with a profound impact on the development and progression of CVDs. In this review, we briefly describe basic mechanisms of TI and summarize animal studies which specifically focus on TI in the context of CVDs.<\/jats:p>","DOI":"10.3390\/ijms25042312","type":"journal-article","created":{"date-parts":[[2024,2,15]],"date-time":"2024-02-15T08:29:37Z","timestamp":1707985777000},"page":"2312","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Trained Innate Immunity in Animal Models of Cardiovascular Diseases"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-8917-4229","authenticated-orcid":false,"given":"Patricia","family":"Kleimann","sequence":"first","affiliation":[{"name":"Institute of Molecular Cardiology, Faculty of Medicine, University Hospital, Heinrich-Heine-University, 40225 D\u00fcsseldorf, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisa-Marie","family":"Irschfeld","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Faculty of Medicine, University Hospital, Heinrich-Heine-University, 40225 D\u00fcsseldorf, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Grandoch","sequence":"additional","affiliation":[{"name":"Institute of Translational Pharmacology, Faculty of Medicine, University Hospital, Heinrich-Heine-University, 40225 D\u00fcsseldorf, Germany"},{"name":"Cardiovascular Research Institute D\u00fcsseldorf (CARID), University Hospital, 40225 D\u00fcsseldorf, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ulrich","family":"Fl\u00f6gel","sequence":"additional","affiliation":[{"name":"Institute of Molecular Cardiology, Faculty of Medicine, University Hospital, Heinrich-Heine-University, 40225 D\u00fcsseldorf, Germany"},{"name":"Cardiovascular Research Institute D\u00fcsseldorf (CARID), University Hospital, 40225 D\u00fcsseldorf, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8807-2767","authenticated-orcid":false,"given":"Sebastian","family":"Temme","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Institute D\u00fcsseldorf (CARID), University Hospital, 40225 D\u00fcsseldorf, Germany"},{"name":"Department of Anesthesiology, Faculty of Medicine, University Hospital, Heinrich-Heine-University, 40225 D\u00fcsseldorf, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,2,15]]},"reference":[{"key":"ref_1","first-page":"1","article-title":"Pattern Recognition Receptors in Health and Diseases","volume":"6","author":"Li","year":"2021","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1038\/nrg1489","article-title":"Gene Map of the Extended Human MHC","volume":"5","author":"Horton","year":"2004","journal-title":"Nat. Rev. Genet."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.coi.2006.11.009","article-title":"Autophagy in MHC Class II Antigen Processing","volume":"19","author":"Strawbridge","year":"2007","journal-title":"Curr. Opin. Immunol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1643","DOI":"10.3389\/fimmu.2018.01643","article-title":"Current Concepts of Antigen Cross-Presentation","volume":"9","author":"Embgenbroich","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"104212","DOI":"10.1016\/j.cellimm.2020.104212","article-title":"CD8+ T Cells: The Past and Future of Immune Regulation","volume":"357","author":"Lees","year":"2020","journal-title":"Cell. Immunol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1016\/j.smim.2007.10.007","article-title":"Th17 Cells: Effector T Cells with Inflammatory Properties","volume":"19","author":"Korn","year":"2007","journal-title":"Semin. Immunol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1146\/annurev.immunol.25.022106.141623","article-title":"Regulatory T Cells: Mechanisms of Differentiation and Function","volume":"30","author":"Josefowicz","year":"2012","journal-title":"Annu. Rev. Immunol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1146\/annurev-immunol-041015-055605","article-title":"Follicular Helper T Cells","volume":"34","author":"Vinuesa","year":"2016","journal-title":"Annu. Rev. Immunol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1152\/physrev.00023.2001","article-title":"Dendritic Cells: Immune Regulators in Health and Disease","volume":"82","author":"Lipscomb","year":"2002","journal-title":"Physiol. Rev."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1038\/s41577-020-0285-6","article-title":"Defining Trained Immunity and Its Role in Health and Disease","volume":"20","author":"Netea","year":"2020","journal-title":"Nat. Rev. Immunol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1161\/ATVBAHA.120.314212","article-title":"Trained Immunity: Long-Term Adaptation in Innate Immune Responses","volume":"41","author":"Tercan","year":"2021","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.cell.2017.11.034","article-title":"Modulation of Myelopoiesis Progenitors Is an Integral Component of Trained Immunity","volume":"172","author":"Mitroulis","year":"2018","journal-title":"Cell"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Riksen, N.P., Bekkering, S., Mulder, W.J.M., and Netea, M.G. (2023). Trained Immunity in Atherosclerotic Cardiovascular Disease. Nat. Rev. Cardiol., 1\u201313.","DOI":"10.1038\/s41569-023-00894-y"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1146\/annurev-immunol-102119-073855","article-title":"Trained Immunity: Reprogramming Innate Immunity in Health and Disease","volume":"39","author":"Bekkering","year":"2021","journal-title":"Annu. Rev. Immunol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s12026-021-09170-y","article-title":"Trained Innate Immunity","volume":"69","author":"Arneth","year":"2021","journal-title":"Immunol. Res."},{"key":"ref_16","first-page":"1000","article-title":"Respiratory Epithelial Cells Can Remember Infection: A Proof-of-Concept Study","volume":"221","author":"Bigot","year":"2020","journal-title":"J. Infect. Dis."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e69951","DOI":"10.7554\/eLife.69951","article-title":"Vaccination Induces Rapid Protection against Bacterial Pneumonia via Training Alveolar Macrophage in Mice","volume":"10","author":"Gu","year":"2021","journal-title":"eLife"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Zughaier, S.M., Rouquette-Loughlin, C.E., and Shafer, W.M. (2020). Identification of a Neisseria Gonorrhoeae Histone Deacetylase: Epigenetic Impact on Host Gene Expression. Pathog. Basel Switz., 9.","DOI":"10.3390\/pathogens9020132"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1038\/nature05762","article-title":"Herpesvirus Latency Confers Symbiotic Protection from Bacterial Infection","volume":"447","author":"Barton","year":"2007","journal-title":"Nature"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"6588","DOI":"10.1038\/ncomms7588","article-title":"Trained Immunity in Newborn Infants of HBV-Infected Mothers","volume":"6","author":"Hong","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.chom.2012.06.006","article-title":"Candida albicans Infection Affords Protection against Reinfection via Functional Reprogramming of Monocytes","volume":"12","author":"Quintin","year":"2012","journal-title":"Cell Host Microbe"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2955","DOI":"10.1038\/s41467-019-10486-5","article-title":"Induction of Memory-like Dendritic Cell Responses in Vivo","volume":"10","author":"Hole","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_23","first-page":"1243","article-title":"Cutting Edge: Plasmodium falciparum Induces Trained Innate Immunity","volume":"200","author":"Schrum","year":"2018","journal-title":"J. Immunol. Baltim. Md 1950"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.chom.2017.12.010","article-title":"BCG Vaccination Protects against Experimental Viral Infection in Humans through the Induction of Cytokines Associated with Trained Immunity","volume":"23","author":"Arts","year":"2018","journal-title":"Cell Host Microbe"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/j.clim.2014.10.005","article-title":"BCG-Induced Trained Immunity in NK Cells: Role for Non-Specific Protection to Infection","volume":"155","author":"Kleinnijenhuis","year":"2014","journal-title":"Clin. Immunol. Orlando Fla"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"874","DOI":"10.1038\/s41467-019-08659-3","article-title":"Outcomes of Controlled Human Malaria Infection after BCG Vaccination","volume":"10","author":"Walk","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"eaau6849","DOI":"10.1126\/sciadv.aau6849","article-title":"Nonspecific Effects of Oral Vaccination with Live-Attenuated Salmonella Typhi Strain Ty21a","volume":"5","author":"Pennington","year":"2019","journal-title":"Sci. Adv."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1136\/bmj.311.7003.481","article-title":"Non-Specific Beneficial Effect of Measles Immunisation: Analysis of Mortality Studies from Developing Countries","volume":"311","author":"Aaby","year":"1995","journal-title":"BMJ"},{"key":"ref_29","first-page":"695","article-title":"Vaccinations against Smallpox and Tuberculosis Are Associated with Better Long-Term Survival: A Danish Case-Cohort Study 1971-2010","volume":"46","author":"Rieckmann","year":"2017","journal-title":"Int. J. Epidemiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e596","DOI":"10.1093\/cid\/ciaa1351","article-title":"National Immunization Campaigns With Oral Polio Vaccine May Reduce All-Cause Mortality: An Analysis of 13 Years of Demographic Surveillance Data From an Urban African Area","volume":"72","author":"Andersen","year":"2021","journal-title":"Clin. Infect. Dis. Off. Publ. Infect. Dis. Soc. Am."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Debisarun, P.A., G\u00f6ssling, K.L., Bulut, O., Kilic, G., Zoodsma, M., Liu, Z., Oldenburg, M., R\u00fcchel, N., Zhang, B., and Xu, C.-J. (2021). Induction of Trained Immunity by Influenza Vaccination-Impact on COVID-19. PLoS Pathog., 17.","DOI":"10.1101\/2021.09.03.21263028"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"C429","DOI":"10.1152\/ajpcell.00130.2023","article-title":"Moderate Exercise Induces Trained Immunity in Macrophages","volume":"325","author":"Murugathasan","year":"2023","journal-title":"Am. J. Physiol.-Cell Physiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e139298","DOI":"10.1172\/JCI139298","article-title":"Lymphocyte Crosstalk Is Required for Monocyte-Intrinsic Trained Immunity to Plasmodium falciparum","volume":"132","author":"Crabtree","year":"2022","journal-title":"J. Clin. Investig."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Lajqi, T., Braun, M., Kranig, S.A., Frommhold, D., P\u00f6schl, J., and Hudalla, H. (2021). LPS Induces Opposing Memory-like Inflammatory Responses in Mouse Bone Marrow Neutrophils. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22189803"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1731","DOI":"10.1161\/ATVBAHA.114.303887","article-title":"Oxidized Low-Density Lipoprotein Induces Long-Term Proinflammatory Cytokine Production and Foam Cell Formation via Epigenetic Reprogramming of Monocytes","volume":"34","author":"Bekkering","year":"2014","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1136\/annrheumdis-2014-206564","article-title":"Soluble Uric Acid Primes TLR-Induced Proinflammatory Cytokine Production by Human Primary Cells via Inhibition of IL-1Ra","volume":"75","author":"Cleophas","year":"2016","journal-title":"Ann. Rheum. Dis."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1016\/j.cmet.2016.10.008","article-title":"Glutaminolysis and Fumarate Accumulation Integrate Immunometabolic and Epigenetic Programs in Trained Immunity","volume":"24","author":"Arts","year":"2016","journal-title":"Cell Metab."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2562","DOI":"10.1016\/j.celrep.2016.11.011","article-title":"Immunometabolic Pathways in BCG-Induced Trained Immunity","volume":"17","author":"Arts","year":"2016","journal-title":"Cell Rep."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.cell.2017.11.025","article-title":"Metabolic Induction of Trained Immunity through the Mevalonate Pathway","volume":"172","author":"Bekkering","year":"2018","journal-title":"Cell"},{"key":"ref_40","first-page":"317","article-title":"Aldosterone Induces Trained Immunity: The Role of Fatty Acid Synthesis","volume":"116","author":"Keating","year":"2020","journal-title":"Cardiovasc. Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1161\/CIRCRESAHA.119.315800","article-title":"Catecholamines Induce Trained Immunity in Monocytes In Vitro and In Vivo","volume":"127","author":"Groh","year":"2020","journal-title":"Circ. Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1128\/CVI.00349-16","article-title":"In Vitro Experimental Model of Trained Innate Immunity in Human Primary Monocytes","volume":"23","author":"Bekkering","year":"2016","journal-title":"Clin. Vaccine Immunol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1251086","DOI":"10.1126\/science.1251086","article-title":"Epigenetic Programming of Monocyte-to-Macrophage Differentiation and Trained Innate Immunity","volume":"345","author":"Saeed","year":"2014","journal-title":"Science"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2040238","DOI":"10.1080\/21645515.2022.2040238","article-title":"Prophylactic and Therapeutic Insights into Trained Immunity: A Renewed Concept of Innate Immune Memory","volume":"18","author":"Bindu","year":"2022","journal-title":"Hum. Vaccines Immunother."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.molimm.2015.06.019","article-title":"Trained Immunity: A Smart Way to Enhance Innate Immune Defence","volume":"68","author":"Joosten","year":"2015","journal-title":"Mol. Immunol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1250684","DOI":"10.1126\/science.1250684","article-title":"mTOR- and HIF-1\u03b1\u2013Mediated Aerobic Glycolysis as Metabolic Basis for Trained Immunity","volume":"345","author":"Cheng","year":"2014","journal-title":"Science"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1869","DOI":"10.1093\/infdis\/jiz692","article-title":"Trained Immunity Confers Broad-Spectrum Protection Against Bacterial Infections","volume":"222","author":"Ciarlo","year":"2020","journal-title":"J. Infect. Dis."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1147476","DOI":"10.3389\/fimmu.2023.1147476","article-title":"Trained Immunity: A \u201cNew\u201d Weapon in the Fight against Infectious Diseases","volume":"14","author":"Dagenais","year":"2023","journal-title":"Front. Immunol."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Mitroulis, I., Hajishengallis, G., and Chavakis, T. (2023). Bone Marrow Inflammatory Memory in Cardiometabolic Disease and Inflammatory Comorbidities. Cardiovasc. Res., cvad003.","DOI":"10.1093\/cvr\/cvad003"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1161\/ATVBAHA.120.314215","article-title":"Trained Immunity and Cardiometabolic Disease: The Role of Bone Marrow","volume":"41","author":"Mitroulis","year":"2021","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"613780","DOI":"10.3389\/fphar.2020.613780","article-title":"Overview of OxLDL and Its Impact on Cardiovascular Health: Focus on Atherosclerosis","volume":"11","author":"Poznyak","year":"2020","journal-title":"Front. Pharmacol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1242","DOI":"10.1161\/CIRCRESAHA.120.315936","article-title":"Modifiable Cardiovascular Risk, Hematopoiesis, and Innate Immunity","volume":"126","author":"Schloss","year":"2020","journal-title":"Circ. Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1038\/s41581-022-00621-9","article-title":"Targeting Innate Immunity-Driven Inflammation in CKD and Cardiovascular Disease","volume":"18","author":"Speer","year":"2022","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"3155","DOI":"10.3389\/fimmu.2018.03155","article-title":"mTOR-Dependent Oxidative Stress Regulates oxLDL-Induced Trained Innate Immunity in Human Monocytes","volume":"9","author":"Sohrabi","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1084\/jem.20150900","article-title":"The Glycolytic Enzyme PKM2 Bridges Metabolic and Inflammatory Dysfunction in Coronary Artery Disease","volume":"213","author":"Shirai","year":"2016","journal-title":"J. Exp. Med."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Piacentini, L., Vavassori, C., and Colombo, G.I. (2022). Trained Immunity in Perivascular Adipose Tissue of Abdominal Aortic Aneurysm\u2014A Novel Concept for a Still Elusive Disease. Front. Cell Dev. Biol., 10.","DOI":"10.3389\/fcell.2022.886086"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1002\/JLB.3AB1220-846R","article-title":"Immune Modulatory Effects of Progesterone on oxLDL-Induced Trained Immunity in Monocytes","volume":"112","author":"Groh","year":"2022","journal-title":"J. Leukoc. Biol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"706583","DOI":"10.3389\/fimmu.2021.706583","article-title":"The Effects of Trained Innate Immunity on T Cell Responses; Clinical Implications and Knowledge Gaps for Future Research","volume":"12","author":"Murphy","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"5670","DOI":"10.1038\/s41467-019-13636-x","article-title":"Trained Immunity Modulates Inflammation-Induced Fibrosis","volume":"10","author":"Jeljeli","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1634","DOI":"10.1016\/j.cell.2018.09.042","article-title":"Induction of Autonomous Memory Alveolar Macrophages Requires T Cell Help and Is Critical to Trained Immunity","volume":"175","author":"Yao","year":"2018","journal-title":"Cell"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Lin, J., Huang, L., Li, Y., Zhang, P., Yu, Q., and Yang, Q. (2021). Bacillus Subtilis Spore-Trained Dendritic Cells Enhance the Generation of Memory T Cells via ICAM1. Cells, 10.","DOI":"10.3390\/cells10092267"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"e57164","DOI":"10.15252\/embr.202357164","article-title":"Trained Immunity Induced by High-Salt Diet Impedes Stroke Recovery","volume":"24","author":"Lin","year":"2023","journal-title":"EMBO Rep."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1038\/nature11868","article-title":"Sodium Chloride Drives Autoimmune Disease by the Induction of Pathogenic TH17 Cells","volume":"496","author":"Kleinewietfeld","year":"2013","journal-title":"Nature"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/j.cmet.2023.01.009","article-title":"Sodium Perturbs Mitochondrial Respiration and Induces Dysfunctional Tregs","volume":"35","author":"Hamad","year":"2023","journal-title":"Cell Metab."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.1161\/CIRCRESAHA.115.308111","article-title":"CD70 Exacerbates Blood Pressure Elevation and Renal Damage in Response to Repeated Hypertensive Stimuli","volume":"118","author":"Itani","year":"2016","journal-title":"Circ. Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2812","DOI":"10.1097\/CM9.0000000000002875","article-title":"Regulatory T Cells and Cardiovascular Diseases","volume":"136","author":"Hu","year":"2023","journal-title":"Chin. Med. J."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Hinkley, H., Counts, D.A., VonCanon, E., and Lacy, M. (2023). T Cells in Atherosclerosis: Key Players in the Pathogenesis of Vascular Disease. Cells, 12.","DOI":"10.3390\/cells12172152"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1146\/annurev-immunol-042617-053104","article-title":"The Emerging Role of B Lymphocytes in Cardiovascular Disease","volume":"38","author":"Adamo","year":"2020","journal-title":"Annu. Rev. Immunol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1352","DOI":"10.1055\/s-0038-1666860","article-title":"Inflammasome, T Lymphocytes and Innate-Adaptive Immunity Crosstalk: Role in Cardiovascular Disease and Therapeutic Perspectives","volume":"118","author":"Pedicino","year":"2018","journal-title":"Thromb. Haemost."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1038\/s41577-021-00584-1","article-title":"How the Immune System Shapes Atherosclerosis: Roles of Innate and Adaptive Immunity","volume":"22","author":"Roy","year":"2022","journal-title":"Nat. Rev. Immunol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"2202","DOI":"10.1096\/fj.13-243105","article-title":"Hypercholesterolemia-Induced Priming of Hematopoietic Stem and Progenitor Cells Aggravates Atherosclerosis","volume":"28","author":"Seijkens","year":"2014","journal-title":"FASEB J."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/j.cell.2017.12.013","article-title":"Western Diet Triggers NLRP3-Dependent Innate Immune Reprogramming","volume":"172","author":"Christ","year":"2018","journal-title":"Cell"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1161\/CIRCULATIONAHA.120.046464","article-title":"Hyperglycemia Induces Trained Immunity in Macrophages and Their Precursors and Promotes Atherosclerosis","volume":"144","author":"Edgar","year":"2021","journal-title":"Circulation"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"13436","DOI":"10.1038\/ncomms13436","article-title":"The Persistence of Low-Grade Inflammatory Monocytes Contributes to Aggravated Atherosclerosis","volume":"7","author":"Geng","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1268916","DOI":"10.3389\/fimmu.2023.1268916","article-title":"ER Stress Mediates Angiotensin II-Augmented Innate Immunity Memory and Facilitates Distinct Susceptibilities of Thoracic from Abdominal Aorta to Aneurysm Development","volume":"14","author":"Lu","year":"2023","journal-title":"Front. Immunol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"858256","DOI":"10.3389\/fimmu.2022.858256","article-title":"Aorta in Pathologies May Function as an Immune Organ by Upregulating Secretomes for Immune and Vascular Cell Activation, Differentiation and Trans-Differentiation-Early Secretomes May Serve as Drivers for Trained Immunity","volume":"13","author":"Lu","year":"2022","journal-title":"Front. Immunol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1452","DOI":"10.1038\/s41591-020-0964-7","article-title":"Myocardial Infarction Accelerates Breast Cancer via Innate Immune Reprogramming","volume":"26","author":"Koelwyn","year":"2020","journal-title":"Nat. Med."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1002\/iub.2425","article-title":"An Overview of the Innate and Adaptive Immune System in Atherosclerosis","volume":"73","author":"Arefnezhad","year":"2021","journal-title":"IUBMB Life"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.tem.2012.10.008","article-title":"Hypercholesterolemia Links Hematopoiesis with Atherosclerosis","volume":"24","author":"Soehnlein","year":"2013","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Feng, Y., Schouteden, S., Geenens, R., Duppen, V.V., Herijgers, P., Holvoet, P., Veldhoven, P.P.V., and Verfaillie, C.M. (2012). Hematopoietic Stem\/Progenitor Cell Proliferation and Differentiation Is Differentially Regulated by High-Density and Low-Density Lipoproteins in Mice. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0047286"},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Itabe, H., and Obama, T. (2023). The Oxidized Lipoproteins In Vivo: Its Diversity and Behavior in the Human Circulation. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24065747"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1875","DOI":"10.1016\/j.cca.2010.08.038","article-title":"Mechanisms of LDL Oxidation","volume":"411","author":"Yoshida","year":"2010","journal-title":"Clin. Chim. Acta"},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Poznyak, A., Grechko, A.V., Poggio, P., Myasoedova, V.A., Alfieri, V., and Orekhov, A.N. (2020). The Diabetes Mellitus\u2013Atherosclerosis Connection: The Role of Lipid and Glucose Metabolism and Chronic Inflammation. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21051835"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/j.ijmm.2007.04.001","article-title":"Structural Biology of the LPS Recognition","volume":"297","author":"Jerala","year":"2007","journal-title":"Int. J. Med. Microbiol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1189\/jlb.3RU0316-151R","article-title":"Endotoxemia\u2014Menace, Marker, or Mistake?","volume":"100","author":"Munford","year":"2016","journal-title":"J. Leukoc. Biol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1354","DOI":"10.1016\/j.cell.2016.09.034","article-title":"\u03b2-Glucan Reverses the Epigenetic State of LPS-Induced Immunological Tolerance","volume":"167","author":"Novakovic","year":"2016","journal-title":"Cell"},{"key":"ref_87","first-page":"e37","article-title":"Aortic Aneurysms and Dissections Series","volume":"40","author":"Shen","year":"2020","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1038\/nrcardio.2017.52","article-title":"Monocytes and Macrophages in Abdominal Aortic Aneurysm","volume":"14","author":"Raffort","year":"2017","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"555","DOI":"10.4070\/kcj.2020.0042","article-title":"Sodium Intake, Blood Pressure and Cardiovascular Disease","volume":"50","author":"Rhee","year":"2020","journal-title":"Korean Circ. J."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"e13250","DOI":"10.1111\/cpr.13250","article-title":"The Modulatory Effect of High Salt on Immune Cells and Related Diseases","volume":"55","author":"Li","year":"2022","journal-title":"Cell Prolif."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1038\/s41577-018-0113-4","article-title":"Sodium in the Microenvironment Regulates Immune Responses and Tissue Homeostasis","volume":"19","author":"Wilck","year":"2019","journal-title":"Nat. Rev. Immunol."},{"key":"ref_92","unstructured":"Wenstedt, E.F.E., Verberk, S.G.S., Kroon, J., Neele, A.E., Baardman, J., Claessen, N., Pasaoglu, \u00d6.T., Rademaker, E., Schrooten, E.M., and Wouda, R.D. (2022, July 06). Salt Increases Monocyte CCR2 Expression and Inflammatory Responses in Humans. Available online: https:\/\/insight.jci.org\/articles\/view\/130508\/sd\/1."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.trsl.2014.11.007","article-title":"Effects of Dietary Salt Levels on Monocytic Cells and Immune Responses in Healthy Human Subjects: A Longitudinal Study","volume":"166","author":"Yi","year":"2015","journal-title":"Transl. Res."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1358","DOI":"10.1093\/cvr\/cvaa207","article-title":"Sodium Activates Human Monocytes via the NADPH Oxidase and Isolevuglandin Formation","volume":"117","author":"Xiao","year":"2021","journal-title":"Cardiovasc. Res."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.jaut.2015.11.001","article-title":"Sodium Chloride Promotes Pro-Inflammatory Macrophage Polarization Thereby Aggravating CNS Autoimmunity","volume":"67","author":"Hucke","year":"2016","journal-title":"J. Autoimmun."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1038\/nature24628","article-title":"Salt-Responsive Gut Commensal Modulates TH17 Axis and Disease","volume":"551","author":"Wilck","year":"2017","journal-title":"Nature"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"104923","DOI":"10.1016\/j.neuint.2020.104923","article-title":"Brain Injury and Repair after Intracerebral Hemorrhage: The Role of Microglia and Brain-Infiltrating Macrophages","volume":"142","author":"Dasari","year":"2021","journal-title":"Neurochem. Int."},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Herring, J.A., Elison, W.S., and Tessem, J.S. (2019). Function of Nr4a Orphan Nuclear Receptors in Proliferation, Apoptosis and Fuel Utilization Across Tissues. Cells, 8.","DOI":"10.3390\/cells8111373"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"874182","DOI":"10.3389\/fmed.2022.874182","article-title":"NR4A1-3 Nuclear Receptor Activity and Immune Cell Dysregulation in Rheumatic Diseases","volume":"9","author":"Murphy","year":"2022","journal-title":"Front. Med."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1016\/j.jaccao.2023.01.010","article-title":"Risk of Cancer After Diagnosis of Cardiovascular Disease","volume":"5","author":"Bell","year":"2023","journal-title":"JACC CardioOncology"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"583084","DOI":"10.3389\/fimmu.2020.583084","article-title":"Tumor-Associated Macrophages in Tumor Immunity","volume":"11","author":"Pan","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_102","first-page":"305","article-title":"Systemic Inflammatory Response Following Acute Myocardial Infarction","volume":"12","author":"Fang","year":"2015","journal-title":"J. Geriatr. Cardiol. JGC"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1038\/s41388-020-01560-0","article-title":"Insights from Transgenic Mouse Models of PyMT-Induced Breast Cancer: Recapitulating Human Breast Cancer Progression in Vivo","volume":"40","author":"Attalla","year":"2021","journal-title":"Oncogene"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1038\/s44161-022-00210-w","article-title":"Non-Invasive Mapping of Systemic Neutrophil Dynamics upon Cardiovascular Injury","volume":"2","author":"Bouvain","year":"2023","journal-title":"Nat. Cardiovasc. Res."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1209","DOI":"10.1038\/s41593-018-0213-2","article-title":"Direct Vascular Channels Connect Skull Bone Marrow and the Brain Surface Enabling Myeloid Cell Migration","volume":"21","author":"Herisson","year":"2018","journal-title":"Nat. Neurosci."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"dev200270","DOI":"10.1242\/dev.200270","article-title":"Biology of Resident Tissue Macrophages","volume":"149","author":"Lee","year":"2022","journal-title":"Development"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1038\/s41586-018-0023-4","article-title":"Innate Immune Memory in the Brain Shapes Neurological Disease Hallmarks","volume":"556","author":"Wendeln","year":"2018","journal-title":"Nature"},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"Ciesielski, O., Biesiekierska, M., Panthu, B., Vialichka, V., Pirola, L., and Balcerczyk, A. (2020). The Epigenetic Profile of Tumor Endothelial Cells. Effects of Combined Therapy with Antiangiogenic and Epigenetic Drugs on Cancer Progression. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21072606"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"3615","DOI":"10.1016\/j.ygeno.2020.04.022","article-title":"Genetic and Epigenetic Stability of Stem Cells: Epigenetic Modifiers Modulate the Fate of Mesenchymal Stem Cells","volume":"112","author":"Sharma","year":"2020","journal-title":"Genomics"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"107701","DOI":"10.1016\/j.celrep.2020.107701","article-title":"Epigenetic Reprogramming of Cancer-Associated Fibroblasts Deregulates Glucose Metabolism and Facilitates Progression of Breast Cancer","volume":"31","author":"Becker","year":"2020","journal-title":"Cell Rep."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"719456","DOI":"10.3389\/fgene.2021.719456","article-title":"Epigenetic Regulation of Vascular Smooth Muscle Cell Phenotype Switching in Atherosclerotic Artery Remodeling: A Mini-Review","volume":"12","author":"Zurek","year":"2021","journal-title":"Front. Genet."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"2409","DOI":"10.1084\/jem.20081188","article-title":"Transient High Glucose Causes Persistent Epigenetic Changes and Altered Gene Expression during Subsequent Normoglycemia","volume":"205","author":"Brasacchio","year":"2008","journal-title":"J. Exp. Med."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"13","DOI":"10.3389\/fimmu.2019.00013","article-title":"Mechanisms of Trained Innate Immunity in oxLDL Primed Human Coronary Smooth Muscle Cells","volume":"10","author":"Schnack","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"5551","DOI":"10.1113\/jphysiol.2009.179432","article-title":"Exercise Protects the Cardiovascular System: Effects beyond Traditional Risk Factors","volume":"587","author":"Joyner","year":"2009","journal-title":"J. Physiol."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1038\/s42255-021-00402-x","article-title":"Pre-Operative Exercise Therapy Triggers Anti-Inflammatory Trained Immunity of Kupffer Cells through Metabolic Reprogramming","volume":"3","author":"Zhang","year":"2021","journal-title":"Nat. Metab."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/4\/2312\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:00:12Z","timestamp":1760104812000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/4\/2312"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,15]]},"references-count":115,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2024,2]]}},"alternative-id":["ijms25042312"],"URL":"https:\/\/doi.org\/10.3390\/ijms25042312","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,2,15]]}}}