{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T16:54:58Z","timestamp":1767200098506,"version":"3.48.0"},"reference-count":128,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T00:00:00Z","timestamp":1766966400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Aberrant signaling pathways of the acquired immune system are implicated in the development of cardiovascular disease (CVD) and chronic kidney disease (CKD) phenotypes. Understanding the complex abnormalities of lymphocyte subpopulations in CKD is a prerequisite for elucidating their implication in uremic cardiomyopathy. T cell subsets display various patterns of association with indices of myocardial function in both experimental and clinical CKD models. The role of Tregs in CVD and CKD has attracted significant research interest. Although experimental data suggest a protective role of Tregs from the development of arterial hypertension- and pressure overload-induced myocardial hypertrophy, there might be a change in the regulatory T cell (Treg) phenotype towards a profibrotic one in the settings of CKD and heart failure. Depletion of B lymphocytes is a hallmark of CKD and heart failure, bearing adverse prognostic significance, yet evidence of B lymphocytes\u2019 involvement in the pathogenesis of myocardial damage is currently lacking. Considering that myocardial remodeling is the final outcome of diverse pathogenic processes targeting the heart, the aim of this review is to present the evidence available up to now regarding the role of acquired immune cells in the pathogenesis of the structural and functional alterations of the myocardium in CKD.<\/jats:p>","DOI":"10.3390\/biom16010049","type":"journal-article","created":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T16:08:00Z","timestamp":1767197280000},"page":"49","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Signaling Pathways of the Acquired Immune System and Myocardial Dysfunction in Chronic Kidney Disease\u2014What Do We Know So Far?"],"prefix":"10.3390","volume":"16","author":[{"given":"Anila","family":"Duni","sequence":"first","affiliation":[{"name":"Department of Nephrology, Faculty of Medicine, School of Health Sciences, University Hospital of Ioannina, University of Ioannina, 45500 Ioannina, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-8037-1956","authenticated-orcid":false,"given":"Christos","family":"Georgopoulos","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Faculty of Medicine, School of Health Sciences, University Hospital of Ioannina, University of Ioannina, 45500 Ioannina, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Athanasios","family":"Kitsos","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Faculty of Medicine, School of Health Sciences, University Hospital of Ioannina, University of Ioannina, 45500 Ioannina, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7700-7003","authenticated-orcid":false,"given":"Georgios","family":"Markopoulos","sequence":"additional","affiliation":[{"name":"Laboratory of Hematology-Unit of Molecular Biology and Translational Flow Cytometry, University Hospital of Ioannina, 45500 Ioannina, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lefkothea","family":"Dova","sequence":"additional","affiliation":[{"name":"Laboratory of Hematology-Unit of Molecular Biology and Translational Flow Cytometry, University Hospital of Ioannina, 45500 Ioannina, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3884-4965","authenticated-orcid":false,"given":"Georgios","family":"Vartholomatos","sequence":"additional","affiliation":[{"name":"Laboratory of Hematology-Unit of Molecular Biology and Translational Flow Cytometry, University Hospital of Ioannina, 45500 Ioannina, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1172-1829","authenticated-orcid":false,"given":"Evangelia","family":"Dounousi","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Faculty of Medicine, School of Health Sciences, University Hospital of Ioannina, University of Ioannina, 45500 Ioannina, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1038\/sj.ki.5000417","article-title":"Traditional and emerging cardiovascular and renal risk factors: An epidemiologic perspective","volume":"70","author":"Zoccali","year":"2006","journal-title":"Kidney Int."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1938","DOI":"10.2215\/CJN.03500412","article-title":"CRIC Study Investigators. Association between albuminuria, kidney function, and inflammatory biomarker profile in CKD in CRIC","volume":"7","author":"Gupta","year":"2012","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_3","first-page":"2503","article-title":"Immune and inflammatory mechanisms mediate cardiovascular diseases from head to toe","volume":"117","author":"Libby","year":"2021","journal-title":"Cardiovasc. Res."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Provenzano, M., Coppolino, G., De Nicola, L., Serra, R., Garofalo, C., Andreucci, M., and Bolignano, D. (2019). Unraveling Cardiovascular Risk in Renal Patients: A New Take on Old Tale. Front. Cell Dev. Biol., 7.","DOI":"10.3389\/fcell.2019.00314"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1725","DOI":"10.1681\/ASN.2012020145","article-title":"Associations between kidney function and subclinical cardiac abnormalities in CKD","volume":"23","author":"Park","year":"2012","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1093\/eurheartj\/ehp507","article-title":"Acute Dialysis Quality Initiative (ADQI) consensus group. Cardio-renal syndromes: Report from the consensus conference of the acute dialysis quality initiative","volume":"31","author":"Ronco","year":"2010","journal-title":"Eur. Heart J."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1159\/000492731","article-title":"In-hospital mortality and major adverse cardiovascular events after kidney transplantation in the United States","volume":"9","author":"Goyal","year":"2019","journal-title":"Cardiorenal Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"63","DOI":"10.2174\/18756212MTA3yNzEe1","article-title":"The Innate Immune System and Cardiovascular Disease in ESKD: Monocytes and Natural Killer Cells","volume":"19","author":"Dounousi","year":"2021","journal-title":"Curr. Vasc. Pharmacol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2405","DOI":"10.1016\/j.jacc.2018.03.490","article-title":"Inhibition of Interleukin-1\u03b2 by Canakinumab and Cardiovascular Outcomes in Patients with Chronic Kidney Disease","volume":"71","author":"Ridker","year":"2018","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2328","DOI":"10.1038\/s41591-024-03043-1","article-title":"IL-6 inhibition with clazakizumab in patients receiving maintenance dialysis: A randomized phase 2b trial","volume":"30","author":"Chertow","year":"2024","journal-title":"Nat. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1093\/cvr\/cvab113","article-title":"Rituximab in patients with acute ST-elevation myocardial infarction: An experimental medicine safety study","volume":"118","author":"Zhao","year":"2022","journal-title":"Cardiovasc. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1038\/sj.ki.5001550","article-title":"Naive and central memory T-cell lymphopenia in end-stage renal disease","volume":"70","author":"Yoon","year":"2006","journal-title":"Kidney Int."},{"key":"ref_13","first-page":"183","article-title":"T cells and B cells in chronic renal failure","volume":"16","author":"Chatenoud","year":"1996","journal-title":"Semin. Nephrol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1097\/MOT.0000000000000375","article-title":"The effect of chronic kidney disease on T cell alloimmunity","volume":"22","author":"Winterberg","year":"2017","journal-title":"Curr. Opin. Organ Transplant."},{"key":"ref_15","first-page":"255","article-title":"Immune cell dysfunction and inflammation in end-stage renal disease","volume":"9","author":"Betjes","year":"2013","journal-title":"Rev. Nephrol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1111\/j.1525-139X.2007.00283.x","article-title":"Disturbances of acquired immunity in hemodialysis patients","volume":"20","author":"Eleftheriadis","year":"2007","journal-title":"Semin Dial."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1038\/ki.2011.110","article-title":"Premature aging of circulating T cells in patients with end-stage renal disease","volume":"80","author":"Betjes","year":"2011","journal-title":"Kidney Int."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1681\/ASN.V131204","article-title":"Early T cell activation correlates with expression of apoptosis markers in patients with end-stage renal disease","volume":"13","author":"Meier","year":"2002","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.clim.2005.09.007","article-title":"Progressive loss of renal function is associated with activation and depletion of naive T lymphocytes","volume":"118","author":"Litjens","year":"2006","journal-title":"Clin. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1038\/ki.1993.252","article-title":"T cell activation defect in hemodialysis patients: Evidence for a role of theB7\u2044CD28 pathway","volume":"44","author":"Girndt","year":"1993","journal-title":"Kidney Int."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1382","DOI":"10.1046\/j.1523-1755.2001.0590041382.x","article-title":"Defective expression of B7-2 (CD86) on monocytes of dialysis patients correlates to the uremiaassociated immune defect","volume":"59","author":"Girndt","year":"2001","journal-title":"Kidney Int."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Hartzell, S., Bin, S., Cantarelli, C., Haverly, M., Manrique, J., Angeletti, A., Manna, G., Murphy, B., Zhang, W., and Levitsky, J. (2020). Kidney Failure Associates with T Cell Exhaustion and Imbalanced Follicular Helper T Cells. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.583702"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1689","DOI":"10.1093\/ndt\/gfr010","article-title":"CD4+ CD28null cells are expanded and exhibit a cytolytic profile in end-stage renal disease patients on peritoneal dialysis","volume":"26","author":"Yadav","year":"2011","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1272","DOI":"10.1111\/tri.12416","article-title":"Uremia-associated immunological aging is stably imprinted in the T-cell system and not reversed by kidney transplantation","volume":"27","author":"Meijers","year":"2014","journal-title":"Transpl. Int."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1093\/ndt\/gfv362","article-title":"Long-term CD4 lymphopenia is associated with accelerated decline of kidney allograft function","volume":"31","author":"Luque","year":"2016","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1681\/ASN.2016010053","article-title":"Premature T Cell Senescence in Pediatric CKD","volume":"28","author":"George","year":"2016","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Vagiotas, L., Lioulios, G., Panteli, M., Ouranos, K., Xochelli, A., Kasimatis, E., Nikolaidou, V., Samali, M., Daoudaki, M., and Katsanos, G. (2024). Kidney Transplantation and Cellular Immunity Dynamics: Immune Cell Alterations and Association with Clinical and Laboratory Parameters. J. Clin. Med., 13.","DOI":"10.3390\/jcm13175093"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Leonhard, J., Schaier, M., K\u00e4lble, F., Eckstein, V., Zeier, M., and Steinborn, A. (2022). Chronic Kidney Failure Provokes the Enrichment of Terminally Differentiated CD8+ T Cells, Impairing Cytotoxic Mechanisms After Kidney Transplantation. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.752570"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1681\/ASN.2019080847","article-title":"Terminally Differentiated Effector Memory CD8+ T Cells Identify Kidney Transplant Recipients at High Risk of Graft Failure","volume":"31","author":"Jacquemont","year":"2020","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1016\/j.ajt.2024.10.001","article-title":"Terminally differentiated effector memory T cells in kidney transplant recipients: New crossroads","volume":"25","author":"Glorieux","year":"2025","journal-title":"Am. J. Transplant."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1038\/s41581-023-00733-w","article-title":"Regulatory T cells in autoimmune kidney diseases and transplantation","volume":"19","author":"Mikami","year":"2023","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2731","DOI":"10.1681\/ASN.2005080842","article-title":"CD4\u00feCD25\u00fe regulatory T cells protect against injury in an innate murine model of chronic kidney disease","volume":"17","author":"Mahajan","year":"2006","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2819","DOI":"10.1111\/ajt.12445","article-title":"Infiltrating Foxp3\u00fe regulatory T cells from spontaneously tolerant kidney allografts demonstrate donorspecific tolerance","volume":"13","author":"Hu","year":"2013","journal-title":"Am. J. Transplant."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1969","DOI":"10.1093\/ndt\/gfp005","article-title":"End-stage renal failure and regulatory activities of CD4+ CD25bright+ FoxP3+ T-cells","volume":"24","author":"Hendrikx","year":"2009","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1159\/000471814","article-title":"Hemodialysis Patients Display a Declined Proportion of Th2 and Regulatory T Cells in Parallel with a High Interferon-gamma Profile","volume":"136","author":"Mansouri","year":"2017","journal-title":"Nephron"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1111\/j.1440-1797.2009.01172.x","article-title":"Regulatory T cells\/T-helper cell 17 functional imbalance in uraemic patients on maintenance haemodialysis: A pivotal link between microinflammation and adverse cardiovascular events","volume":"15","author":"Zhang","year":"2010","journal-title":"Nephrology"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1038\/nature04753","article-title":"Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells","volume":"441","author":"Bettelli","year":"2006","journal-title":"Nature"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"6725","DOI":"10.4049\/jimmunol.178.11.6725","article-title":"Cutting edge: Regulatory T cells induce CD4+ CD25- Foxp3- T cells or are self-induced to become Th17 cells in the absence of exogenous TGF-beta","volume":"178","author":"Xu","year":"2007","journal-title":"J. Immunol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1203","DOI":"10.1016\/j.kint.2016.09.043","article-title":"Natural regulatory T cells from patients with end-stage renal disease can be used for large-scale generation of highly suppressive alloantigen-specific Tregs","volume":"91","author":"Litjens","year":"2017","journal-title":"Kidney Int."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1159\/000449242","article-title":"The Influence of Hemodialysis on T Regulatory Cells: A Meta-Analysis and Systematic Review","volume":"42","author":"Caprara","year":"2016","journal-title":"Blood Purif."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"37","DOI":"10.5414\/CN110158","article-title":"Differential effects of peritoneal and hemodialysis on circulating regulatory T cells one month post initiation of renal replacement therapy","volume":"95","author":"Caprara","year":"2021","journal-title":"Clin. Nephrol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1760","DOI":"10.2215\/CJN.01750218","article-title":"Regulatory T Cells and Kidney Transplantation","volume":"13","author":"Tripathi","year":"2018","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1111\/imm.12947","article-title":"End-stage renal disease, dialysis, kidney transplantation and their impact on CD4+ T-cell differentiation","volume":"155","author":"Schaier","year":"2018","journal-title":"Immunology"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"91","DOI":"10.3324\/haematol.2015.128934","article-title":"Impact of immunosuppressive drugs on the therapeutic efficacy of ex vivo expanded human regulatory T cells","volume":"101","author":"Fanelli","year":"2016","journal-title":"Haematologica"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Schaier, M., Seissler, N., Schmitt, E., Meuer, S., Hug, F., Zeier, M., and Steinborn, A. (2012). DR(high+)CD45RA(\u2212)-Tregs potentially affect the suppressive activity of the total Treg pool in renal transplant patients. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0034208"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1016\/j.kint.2016.03.022","article-title":"Regulatory T cells in kidney disease and transplantation","volume":"90","author":"Hu","year":"2016","journal-title":"Kidney Int."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1093\/ndt\/gfp397","article-title":"Effect of end-stage renal disease on B lymphocyte subpopulations, 7, BAFF and BAFF receptor expression","volume":"25","author":"Pahl","year":"2010","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1093\/ndt\/15.4.502","article-title":"B lymphopenia in uremia is related to an accelerated in vitro apoptosis and dysregulation of Bcl-2","volume":"15","author":"Ramos","year":"2000","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1111\/j.1365-2249.2004.02571.x","article-title":"Children with chronic renal failure have reduced numbers of memory B cells","volume":"137","author":"Bouts","year":"2004","journal-title":"Clin. Exp. Immunol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"20797","DOI":"10.1038\/s41598-023-47742-0","article-title":"Distribution characteristics of circulating B cell subpopulations in patients with chronic kidney disease","volume":"13","author":"Chen","year":"2023","journal-title":"Sci. Rep."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1146\/annurev.immunol.19.1.595","article-title":"B cell development pathways","volume":"19","author":"Hardy","year":"2001","journal-title":"Annu. Rev. Immunol."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Ciocca, M., Zaffina, S., Fernandez Salinas, A., Bocci, C., Palomba, P., Conti, M.G., Terreri, S., Frisullo, G., Giorda, E., and Scarsella, M. (2021). Evolution of human memory B cells from childhood to old age. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.690534"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1053\/j.jrn.2011.10.020","article-title":"Effect of uremia on structure and function of immune system","volume":"22","author":"Vaziri","year":"2012","journal-title":"J. Ren. Nutr."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"10842","DOI":"10.1038\/s41467-024-55187-w","article-title":"The survival of B cells is compromised in kidney disease","volume":"15","author":"Peroumal","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2141","DOI":"10.4049\/jimmunol.147.7.2141","article-title":"Myosin-induced acute myocarditis is a T cell-mediated disease","volume":"147","author":"Smith","year":"1991","journal-title":"J. Immunol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1652","DOI":"10.1161\/CIRCULATIONAHA.111.044164","article-title":"Activation of CD4+ T lymphocytes improves wound healing and survival after experimental myocardial infarction in mice","volume":"125","author":"Hofmann","year":"2012","journal-title":"Circulation"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2111","DOI":"10.1161\/CIRCULATIONAHA.113.007101","article-title":"CD4+ T cells promote the transition from hypertrophy to heart failure during chronic pressure overload","volume":"129","author":"Laroumanie","year":"2014","journal-title":"Circulation"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.matbio.2020.04.001","article-title":"T cell regulation of fibroblasts and cardiac fibrosis","volume":"91","author":"Bradshaw","year":"2020","journal-title":"Matrix Biol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1016\/j.matbio.2010.06.003","article-title":"T-lymphocytes mediate left ventricular fibrillar collagen cross-linking and diastolic dysfunction in mice","volume":"29","author":"Yu","year":"2010","journal-title":"Matrix Biol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1161\/CIRCHEARTFAILURE.115.002225","article-title":"Left Ventricular T-Cell Recruitment Contributes to the Pathogenesis of Heart Failure","volume":"8","author":"Nevers","year":"2015","journal-title":"Circ. Heart Fail."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1007\/s00395-018-0678-x","article-title":"T-bet deficiency attenuates cardiac remodeling in rats","volume":"113","author":"Ma","year":"2018","journal-title":"Basic Res. Cardiol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"e003126","DOI":"10.1161\/JAHA.115.003126","article-title":"Intercellular adhesion molecule 1 regulates left ventricular leukocyte infiltration, cardiac remodeling, and function in pressure overload-induced heart failure","volume":"5","author":"Salvador","year":"2016","journal-title":"J. Am. Heart Assoc."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"125527","DOI":"10.1172\/jci.insight.125527","article-title":"CXCR3 regulates CD4+ T cell cardiotropism in pressureoverload-induced cardiac dysfunction","volume":"4","author":"Ngwenyama","year":"2019","journal-title":"JCI Insight"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/j.yjmcc.2019.01.005","article-title":"Recent advances in understanding the roles of T cells in pressure overload-induced cardiac hypertrophy and remodeling","volume":"129","author":"Liu","year":"2019","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1320","DOI":"10.1038\/ajh.2009.181","article-title":"Attenuation of angiotensin II induced hypertension and cardiac hypertrophy in transgenic mice overexpressing a type 1 receptor mutant","volume":"22","author":"Ahmad","year":"2009","journal-title":"Am. J. Hypertens."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"F734","DOI":"10.1152\/ajprenal.00454.2010","article-title":"Infiltrating T lymphocytes in the kidney increase oxidative stress and participate in the development of hypertension and renal disease","volume":"300","author":"Guo","year":"2011","journal-title":"Am. J. Physiol.-Ren. Physiol."},{"key":"ref_67","first-page":"10","article-title":"Harrison, DC isoketal-modified proteins activate T cells and promote hypertension","volume":"124","author":"AKirabo","year":"2014","journal-title":"J. Clin. Investig."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"H581","DOI":"10.1152\/ajpheart.00112.2019","article-title":"CD8(+) T-cells negatively regulate inflammation post-myocardial infarction","volume":"317","author":"Ilatovskaya","year":"2019","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Komai, K., Ito, M., Nomura, S., Shichino, S., Katoh, M., Yamada, S., Ko, T., Iizuka-Koga, M., Nakatsukasa, H., and Yoshimura, A. (2021). Single-Cell Analysis Revealed the Role of CD8+ Effector T Cells in Preventing Cardioprotective Macrophage Differentiation in the Early Phase of Heart Failure. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.763647"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"14037","DOI":"10.1038\/ncomms14037","article-title":"CD8+ T cells stimulate Na-Cl co-transporter NCC in distal convoluted tubules leading to saltsensitive hypertension","volume":"8","author":"Liu","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1550","DOI":"10.1161\/CIRCRESAHA.121.320373","article-title":"The IFN\u03b3-PDL1 pathway enhances CD8T-DCT interaction to promote hypertension","volume":"130","author":"Benson","year":"2022","journal-title":"Circ. Res."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"2164","DOI":"10.34067\/KID.0001292022","article-title":"Interferon Gamma contributes to the immune mechanisms of hypertension","volume":"3","author":"Benson","year":"2022","journal-title":"Kidney 360"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1648","DOI":"10.1161\/HYPERTENSIONAHA.121.17447","article-title":"Chronic 3D vascular-immune interface established by coculturing pressurized resistance arteries and immune cells","volume":"78","author":"Carnevale","year":"2021","journal-title":"Hypertension"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1161\/HYPERTENSIONAHA.113.00689","article-title":"Immunosenescent CD8+ T cells and C-X-C chemokine receptor type 3 chemokines are increased in human hypertension","volume":"62","author":"Youn","year":"2013","journal-title":"Hypertension"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1161\/HYPERTENSIONAHA.116.07237","article-title":"Activation of human T cells in hypertension: Studies of humanized mice and hypertensive humans","volume":"68","author":"Itani","year":"2016","journal-title":"Hypertension"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1681\/ASN.2017101138","article-title":"T Cells Play a Causal Role in Diastolic Dysfunction during Uremic Cardiomyopathy","volume":"30","author":"Winterberg","year":"2019","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"e0310122","DOI":"10.1128\/spectrum.03101-22","article-title":"Dysbiosis of Gut Microbiota Contributes to Uremic Cardiomyopathy via Induction of IFNgamma-Producing CD4(+) T Cells Expansion","volume":"11","author":"Han","year":"2023","journal-title":"Microbiol. Spectr."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Duni, A., Kitsos, A., Bechlioulis, A., Lakkas, L., Markopoulos, G., Tatsis, V., Koutlas, V., Tzalavra, E., Baxevanos, G., and Vartholomatos, G. (2024). Identification of Novel Independent Correlations Between Cellular Components of the Immune System and Strain-Related Indices of Myocardial Dysfunction in CKD Patients and Kidney Transplant Recipients Without Established Cardiovascular Disease. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25179162"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"e007427","DOI":"10.1161\/JAHA.117.007427","article-title":"Left ventricular torsion associated with aortic stiffness in hypertension","volume":"7","author":"Gnakamene","year":"2018","journal-title":"J. Am. Heart Assoc."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1093\/ehjci\/jeu229","article-title":"Early detection of subclinical left ventricular myocardial dysfunction in patients with chronic kidney disease","volume":"16","author":"Panoulas","year":"2015","journal-title":"Eur. Heart J.-Cardiovasc. Imaging"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1111\/echo.14570","article-title":"The prognostic role of myocardial strain indices and dipyridamole stress test in renal transplantation patients","volume":"37","author":"Lakkas","year":"2020","journal-title":"Echocardiography"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1136\/hrt.75.3.287","article-title":"Abnormal cytokine profiles in patients with idiopathic dilated cardiomyopathy and their asymptomatic relatives","volume":"75","author":"Marriott","year":"1996","journal-title":"Heart"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.yjmcc.2016.10.007","article-title":"CD4 Foxp3 T-cells contribute to myocardial ischemia-reperfusion injury","volume":"101","author":"Mathes","year":"2016","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1007\/s11897-017-0337-9","article-title":"Inflammation-Cause or Consequence of Heart Failure or Both?","volume":"14","year":"2017","journal-title":"Curr. Heart Fail. Rep."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1172\/JCI114460","article-title":"Adrenergic control of circulating lymphocyte subpopulations. Effects of congestive heart failure, dynamic exercise, and terbutaline treatment","volume":"85","author":"Maisel","year":"1990","journal-title":"J. Clin. Investig."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1161\/CIRCHEARTFAILURE.112.970525","article-title":"Predictive value of low relative lymphocyte count in patients hospitalized for heart failure with reduced ejection fraction: Insights from the EVEREST trial","volume":"5","author":"Vaduganathan","year":"2012","journal-title":"Circ. Heart Fail."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1016\/j.amjcard.2010.12.049","article-title":"Usefulness of total lymphocyte count as predictor of outcome in patients with chronic heart failure","volume":"107","author":"Charach","year":"2011","journal-title":"Am. J. Cardiol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1536\/jhj.45.275","article-title":"Usefulness of the percentage of plasma lymphocytes as a prognostic marker in patients with congestive heart failure","volume":"45","author":"Sakatani","year":"2004","journal-title":"Jpn. Heart J."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1424","DOI":"10.1161\/CIRCULATIONAHA.105.584102","article-title":"The Seattle Heart Failure Model: Prediction of survival in heart failure","volume":"113","author":"Levy","year":"2006","journal-title":"Circulation"},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Duni, A., Kitsos, A., Bechlioulis, A., Markopoulos, G.S., Lakkas, L., Baxevanos, G., Mitsis, M., Vartholomatos, G., Naka, K.K., and Dounousi, E. (2023). Differences in the Profile of Circulating Immune Cell Subsets in Males with Type 2 Cardiorenal Syndrome versus CKD Patients Without Established Cardiovascular Disease. Biomedicines, 11.","DOI":"10.3390\/biomedicines11041029"},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Vernier, I.C.S., Neres-Santos, R.S., Andrade-Oliveira, V., and Carneiro-Ramos, M.S. (2023). Cells. Immune Cells Are Differentially Modulated in the Heart and the Kidney during the Development of Cardiorenal Syndrome 3. Cells, 12.","DOI":"10.3390\/cells12040605"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"111805","DOI":"10.1016\/j.exger.2022.111805","article-title":"B lymphocytes subpopulations are associated with cardiac remodeling in elderly patients with advanced chronic kidney disease","volume":"163","author":"Lin","year":"2022","journal-title":"Exp. Gerontol."},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Yang, M., Peng, B., Zhuang, Q., Li, J., Zhang, P., Liu, H., Zhu, Y., and Ming, Y. (2023). Machine learning-based investigation of the relationship between immune status and left ventricular hypertrophy in patients with end-stage kidney disease. Front. Cardiovasc. Med., 10.","DOI":"10.3389\/fcvm.2023.1187965"},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Molina, M., Allende, L.M., Ramos, L.E., Guti\u00e9rrez, E., Pleguezuelo, D.E., Hern\u00e1ndez, E.R., R\u00edos, F., Fern\u00e1ndez, C., Praga, M., and Morales, E. (2018). CD19+ B-Cells, a New Biomarker of Mortality in Hemodialysis Patients. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.01221"},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Duni, A., Vartholomatos, G., Balafa, O., Ikonomou, M., Tseke, P., Lakkas, L., Rapsomanikis, K.P., Kitsos, A., Theodorou, I., and Pappas, C. (2021). The Association of Circulating CD14++ CD16+ Monocytes, Natural Killer Cells and Regulatory T Cells Subpopulations with Phenotypes of Cardiovascular Disease in a Cohort of Peritoneal Dialysis Patients. Front. Med., 8.","DOI":"10.3389\/fmed.2021.724316"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1038\/nrcardio.2015.169","article-title":"Regulatory T cells in cardiovascular diseases","volume":"13","author":"Meng","year":"2016","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"H1233","DOI":"10.1152\/ajpheart.00328.2014","article-title":"Regulatory T cells are recruited in the infarcted mouse myocardium and may modulate fibroblast phenotype and function","volume":"307","author":"Saxena","year":"2014","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1007\/s00395-011-0232-6","article-title":"Regulatory T cells ameliorate cardiac remodeling after myocardial infarction","volume":"107","author":"Tang","year":"2012","journal-title":"Basic Res. Cardiol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1161\/CIRCRESAHA.115.303895","article-title":"Foxp3+ CD4+ T cells improve healing after myocardial infarction by modulating monocyte\/macrophage differentiation","volume":"115","author":"Weirather","year":"2014","journal-title":"Circ. Res."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1161\/CIRCULATIONAHA.118.036065","article-title":"Dysfunctional and proinflammatory regulatory T-lymphocytes are essential for adverse cardiac remodeling in ischemic cardiomyopathy","volume":"139","author":"Bansal","year":"2019","journal-title":"Circulation"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"6079713","DOI":"10.1155\/2020\/6079713","article-title":"The Prognostic Impact of Circulating Regulatory T Lymphocytes on Mortality in Patients with Ischemic Heart Failure with Reduced Ejection Fraction","volume":"2020","author":"Hammer","year":"2020","journal-title":"Mediat. Inflamm."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1536\/ihj.13-343","article-title":"Prognostic value of circulating regulatory T cells for worsening heart failure in heart failure patients with reduced ejection fraction","volume":"55","author":"Okamoto","year":"2014","journal-title":"Int. Heart J."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1939","DOI":"10.1097\/HJH.0b013e328362feb7","article-title":"CD4+ CD25+ Foxp3 regulatory T cells and vascular dysfunction in hypertension","volume":"31","author":"Kassan","year":"2013","journal-title":"J. Hypertens."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"3088","DOI":"10.1172\/JCI97490","article-title":"Nox2 in regulatory T cells promotes angiotensin II-induced cardiovascular remodeling","volume":"128","author":"Emmerson","year":"2018","journal-title":"J. Clin. Investig."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1161\/HYPERTENSIONAHA.111.181123","article-title":"T regulatory lymphocytes prevent aldosterone-induced vascular injury","volume":"59","author":"Kasal","year":"2012","journal-title":"Hypertension"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"2904","DOI":"10.1161\/CIRCULATIONAHA.108.832782","article-title":"Regulatory T cells ameliorate angiotensin II-induced cardiac damage","volume":"119","author":"Kvakan","year":"2009","journal-title":"Circulation"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1097\/HJH.0000000000000761","article-title":"Deficiency of T-regulatory cells exaggerates angiotensin II-induced microvascular injury by enhancing immune responses","volume":"34","author":"Mian","year":"2016","journal-title":"J. Hypertens."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"2046","DOI":"10.1161\/HYPERTENSIONAHA.123.20481","article-title":"Hypertension-Driven Regulatory T-Cell Perturbations Accelerate Myocardial Ischemia-Reperfusion Injury","volume":"80","author":"Sun","year":"2023","journal-title":"Hypertension"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.1161\/HYPERTENSIONAHA.119.14546","article-title":"Mesenchymal Stem Cell-Derived Extracellular Vesicles Induce Regulatory T Cells to Ameliorate Chronic Kidney Injury","volume":"75","author":"Song","year":"2020","journal-title":"Hypertension"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"1752","DOI":"10.1161\/CIRCULATIONAHA.119.045344","article-title":"CD4(+) T-Cell Endogenous Cystathionine gamma Lyase-Hydrogen Sulfide Attenuates Hypertension by Sulfhydrating Liver Kinase B1 to Promote T Regulatory Cell Differentiation and Proliferation","volume":"142","author":"Cui","year":"2020","journal-title":"Circulation"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/j.jacbts.2022.09.007","article-title":"Immune Profiling Reveals Decreases in Circulating Regulatory and Exhausted T Cells in Human Hypertension","volume":"8","author":"Alexander","year":"2023","journal-title":"JACC Basic Transl. Sci."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.molimm.2024.05.002","article-title":"The roles of B cells in cardiovascular diseases","volume":"171","author":"Ma","year":"2024","journal-title":"Mol. Immunol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"e134700","DOI":"10.1172\/jci.insight.134700","article-title":"Myocardial B cells are a subset of circulating lymphocytes with delayed transit through the heart","volume":"5","author":"Adamo","year":"2020","journal-title":"JCI Insight"},{"key":"ref_114","first-page":"2664","article-title":"The healing myocardium mobilizes a distinct B-cell subset through a CXCL13-CXCR5-dependent mechanism","volume":"117","author":"Heinrichs","year":"2021","journal-title":"Cardiovasc. Res."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"1002","DOI":"10.1007\/s10875-013-9889-y","article-title":"TNF-\u03b1-secreting B cells contribute to myocardial fibrosis in dilated cardiomyopathy","volume":"33","author":"Yu","year":"2013","journal-title":"J. Clin. Immunol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1159\/000488405","article-title":"Defective Circulating Regulatory B Cells in Patients with Dilated Cardiomyopathy","volume":"46","author":"Jiao","year":"2018","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"e002484","DOI":"10.1161\/JAHA.115.002484","article-title":"Full Expression of Cardiomyopathy Is Partly Dependent on B-Cells: A Pathway That Involves Cytokine Activation, Immunoglobulin Deposition, and Activation of Apoptosis","volume":"5","author":"Youker","year":"2016","journal-title":"J. Am. Heart Assoc."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.yjmcc.2025.02.007","article-title":"Experimental pressure overload induces a cardiac neoantigen specific humoral immune response","volume":"201","author":"Smolgovsky","year":"2025","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"1014","DOI":"10.1161\/CIRCULATIONAHA.120.047852","article-title":"Role of IgE-FcepsilonR1 in Pathological Cardiac Remodeling and Dysfunction","volume":"143","author":"Zhao","year":"2021","journal-title":"Circulation"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1161\/CIRCRESAHA.124.325813","article-title":"Spleen-Heart Cross-Talk Through CD23-Mediated Signal Promotes Cardiac Remodeling","volume":"137","author":"Feng","year":"2025","journal-title":"Circ. Res."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1161\/CIRCRESAHA.125.326725","article-title":"Splenic CD23+ B Cells: Preventing Adverse Remodeling by Limiting IgE Production","volume":"137","author":"Smolgovsky","year":"2025","journal-title":"Circ. Res."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"3512","DOI":"10.1002\/ehf2.15382","article-title":"Circulating CD19 B cell count, myocardial injury and clinical outcomes in patients with heart failure","volume":"12","author":"Kobayashi","year":"2025","journal-title":"ESC Heart Fail."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"1381","DOI":"10.1038\/s44161-025-00724-z","article-title":"B cells promote atrial fibrillation via autoantibodies","volume":"4","author":"Yamazoe","year":"2025","journal-title":"Nat. Cardiovasc. Res."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"1387","DOI":"10.1002\/ehf2.12744","article-title":"The role of B cells in heart failure and implications for future immunomodulatory treatment strategies","volume":"7","author":"Castillo","year":"2020","journal-title":"ESC Heart Fail."},{"key":"ref_125","doi-asserted-by":"crossref","unstructured":"Lin, J., Tang, B., Feng, Z., Hao, W., and Hu, W. (2021). Decreased B lymphocytes subpopulations are associated with higher atherosclerotic risk in elderly patients with moderate-to-severe chronic kidney diseases. BMC Nephrol., 22.","DOI":"10.1186\/s12882-021-02613-6"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1016\/j.jacbts.2021.01.006","article-title":"B Cells in Atherosclerosis: Mechanisms and Potential Clinical Applications","volume":"6","author":"Pattarabanjird","year":"2021","journal-title":"JACC Basic Transl. Sci."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"2060","DOI":"10.1016\/S0140-6736(21)00520-1","article-title":"IL-6 inhibition with ziltivekimab in patients at high atherosclerotic risk (RESCUE): A double-blind, randomised, placebo-controlled, phase 2 trial","volume":"397","author":"Ridker","year":"2021","journal-title":"Lancet"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"e022452","DOI":"10.1136\/bmjopen-2018-022452","article-title":"Low-dose interleukin-2 in patients with stable ischaemic heart disease and acute coronary syndromes (LILACS): Protocol and study rationale for a randomised, double-blind, placebo-controlled, phase I\/II clinical trial","volume":"8","author":"Zhao","year":"2018","journal-title":"BMJ Open"}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/16\/1\/49\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T16:30:39Z","timestamp":1767198639000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/16\/1\/49"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,29]]},"references-count":128,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,1]]}},"alternative-id":["biom16010049"],"URL":"https:\/\/doi.org\/10.3390\/biom16010049","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,29]]}}}