{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T02:03:56Z","timestamp":1775181836033,"version":"3.50.1"},"reference-count":64,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2025,4,17]],"date-time":"2025-04-17T00:00:00Z","timestamp":1744848000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,4,17]],"date-time":"2025-04-17T00:00:00Z","timestamp":1744848000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","award":["PG\/21\/10574"],"award-info":[{"award-number":["PG\/21\/10574"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","award":["AA\/18\/2\/34218"],"award-info":[{"award-number":["AA\/18\/2\/34218"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","award":["AA\/18\/2\/34218"],"award-info":[{"award-number":["AA\/18\/2\/34218"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Basic Res Cardiol"],"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>Following myocardial infarction (MI), patients with type 2 diabetes mellitus (T2DM) have poorer prognosis which may be linked to increased susceptibility of coronary microvessels to injury. Interleukin-36 (IL-36) may mediate this injury but its role in the microcirculation of the chronically hyperglycaemic injured heart is unknown. Intravital and laser speckle imaging of the anaesthetised mouse beating heart evaluated the impact of a 16-week high fat diet (HFD)-induced hyperglycaemia\u2009\u00b1\u2009myocardial ischaemia\u2013reperfusion injury (IR) injury on coronary microvessels. Neutrophil\/platelet recruitment, neutrophil extracellular trap formation, cellular necrosis, vascular leakage, vascular tonal changes, functional capillary density, overall ventricular perfusion and levels of circulating inflammatory cytokines were assessed alongside the vasculoprotective ability of an IL-36 receptor antagonist (IL-36Ra). Whether heightened microvessel damage in injured HFD mice was permanent or reversible was investigated after normalising hyperglycaemia through diet reversal (DR). Microcirculatory events assessed were perturbed basally in HFD mice and further after injury. IL-36Ra mitigated these effects and improved infarct size. DR was also beneficial, decreasing neutrophil recruitment to levels below those seen in untreated mice. Mechanistically, benefits of both IL-36Ra and DR could be explained by decreased endothelial oxidative stress and VCAM-1 expression and possibly by raised levels of IL-4\/IL-13. Basal changes in chronically hyperglycaemic coronary microvessels that are heightened in the aftermath of reperfusion may explain the poorer outcomes in MI patients with T2DM. These findings are the first to highlight the specific benefits of IL-36 inhibition and reversing hyperglycaemia through dietary modification on the coronary microcirculation in a preclinical model of T2DM.<\/jats:p>","DOI":"10.1007\/s00395-025-01107-y","type":"journal-article","created":{"date-parts":[[2025,4,17]],"date-time":"2025-04-17T02:24:41Z","timestamp":1744856681000},"page":"509-526","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Impact of chronic hyperglycaemia on the coronary microcirculation \u2013 benefits of targeting IL-36 and diet reversal"],"prefix":"10.1007","volume":"120","author":[{"given":"Juma","family":"El-Awaisi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dean","family":"Kavanagh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silke","family":"Heising","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ina Maria","family":"Schiessl","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simon J.","family":"Cleary","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David J.","family":"Hodson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2960-7829","authenticated-orcid":false,"given":"Neena","family":"Kalia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,4,17]]},"reference":[{"key":"1107_CR1","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1177\/1479164119845612","volume":"16","author":"A Avogaro","year":"2019","unstructured":"Avogaro A, Bonora E, Consoli A, Del Prato S, Genovese S, Giorgino F (2019) Glucose-lowering therapy and cardiovascular outcomes in patients with type 2 diabetes mellitus and acute coronary syndrome. Diab Vasc Dis Res 16:399\u2013414. https:\/\/doi.org\/10.1177\/1479164119845612","journal-title":"Diab Vasc Dis Res"},{"key":"1107_CR2","doi-asserted-by":"publisher","first-page":"4407","DOI":"10.1038\/s41467-023-40037-y","volume":"14","author":"L Bordoni","year":"2023","unstructured":"Bordoni L, Kristensen AM, Sardella D, Kidmose H, Pohl L, Krag SRP, Schiessl IM (2023) Longitudinal tracking of acute kidney injury reveals injury propagation along the nephron. Nat Commun 14:4407. https:\/\/doi.org\/10.1038\/s41467-023-40037-y","journal-title":"Nat Commun"},{"key":"1107_CR3","doi-asserted-by":"publisher","first-page":"576","DOI":"10.1095\/biolreprod.116.145680","volume":"96","author":"AH Bryant","year":"2017","unstructured":"Bryant AH, Spencer-Harty S, Owens SE, Jones RH, Thornton CA (2017) Interleukin 4 and interleukin 13 downregulate the lipopolysaccharide-mediated inflammatory response by human gestation-associated tissues. Biol Reprod 96:576\u2013586. https:\/\/doi.org\/10.1095\/biolreprod.116.145680","journal-title":"Biol Reprod"},{"key":"1107_CR4","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1159\/000500437","volume":"56","author":"K Bumroongthai","year":"2019","unstructured":"Bumroongthai K, Kavanagh D, Genever P, Kalia N (2019) Optimising the myocardial homing and therapeutic efficacy of mesenchymal stem cells using 3D culture and specific sub-populations of bone marrow-derived cells. J Vasc Res 56:54\u201354","journal-title":"J Vasc Res"},{"key":"1107_CR5","doi-asserted-by":"publisher","first-page":"1712","DOI":"10.1111\/febs.14075","volume":"284","author":"DM Clancy","year":"2017","unstructured":"Clancy DM, Henry CM, Sullivan GP, Martin SJ (2017) Neutrophil extracellular traps can serve as platforms for processing and activation of IL-1 family cytokines. FEBS J 284:1712\u20131725. https:\/\/doi.org\/10.1111\/febs.14075","journal-title":"FEBS J"},{"key":"1107_CR6","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20241359","author":"SJ Cleary","year":"2025","unstructured":"Cleary SJ, Qiu L, Seo Y, Baluk P, Liu D, Serwas NK, Taylor CA, Zhang D, Cyster JG, McDonald DM, Krummel MF, Looney MR (2025) Intravital imaging of pulmonary lymphatics in inflammation and metastatic cancer. J Exp Med. https:\/\/doi.org\/10.1084\/jem.20241359","journal-title":"J Exp Med"},{"key":"1107_CR7","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1016\/j.beem.2018.03.009","volume":"32","author":"XG da Silva","year":"2018","unstructured":"da Silva XG, Hodson DJ (2018) Mouse models of peripheral metabolic disease. Best Pract Res Clin Endocrinol Metab 32:299\u2013315. https:\/\/doi.org\/10.1016\/j.beem.2018.03.009","journal-title":"Best Pract Res Clin Endocrinol Metab"},{"key":"1107_CR8","doi-asserted-by":"publisher","DOI":"10.3389\/fcvm.2021.660698","volume":"8","author":"M Dia","year":"2021","unstructured":"Dia M, Paccalet A, Pillot B, Leon C, Ovize M, Crola Da Silva C, Bochaton T, Paillard M (2021) Myocardial ischemia-reperfusion and diabetes: lessons learned from bedside to bench. Front Cardiovasc Med 8:660698. https:\/\/doi.org\/10.3389\/fcvm.2021.660698","journal-title":"Front Cardiovasc Med"},{"key":"1107_CR9","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.678771","volume":"12","author":"R Dowey","year":"2021","unstructured":"Dowey R, Iqbal A, Heller SR, Sabroe I, Prince LR (2021) A bittersweet response to infection in diabetes; targeting neutrophils to modify inflammation and improve host immunity. Front Immunol 12:678771. https:\/\/doi.org\/10.3389\/fimmu.2021.678771","journal-title":"Front Immunol"},{"key":"1107_CR10","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.155236","author":"J El-Awaisi","year":"2022","unstructured":"El-Awaisi J, Kavanagh DP, Rink MR, Weston CJ, Drury NE, Kalia N (2022) Targeting IL-36 improves age-related coronary microcirculatory dysfunction and attenuates myocardial ischemia\/reperfusion injury in mice. JCI Insight. https:\/\/doi.org\/10.1172\/jci.insight.155236","journal-title":"JCI Insight"},{"key":"1107_CR11","doi-asserted-by":"publisher","first-page":"1358472","DOI":"10.3389\/fcvm.2024.1358472","volume":"11","author":"J El-Awaisi","year":"2024","unstructured":"El-Awaisi J, Kavanagh DPJ, Kalia N (2024) Monitoring coronary blood flow by laser speckle contrast imaging after myocardial ischaemia reperfusion injury in adult and aged mice. Front Cardiovasc Med 11:1358472. https:\/\/doi.org\/10.3389\/fcvm.2024.1358472","journal-title":"Front Cardiovasc Med"},{"key":"1107_CR12","doi-asserted-by":"publisher","first-page":"1227499","DOI":"10.3389\/fcvm.2023.1227499","volume":"10","author":"J El-Awaisi","year":"2023","unstructured":"El-Awaisi J, Mitchell JL, Ranasinghe A, Kalia N (2023) Interleukin-36 is vasculoprotective in both sexes despite sex-specific changes in the coronary microcirculation response to IR injury. Front Cardiovasc Med 10:1227499. https:\/\/doi.org\/10.3389\/fcvm.2023.1227499","journal-title":"Front Cardiovasc Med"},{"key":"1107_CR13","doi-asserted-by":"publisher","first-page":"1025","DOI":"10.1002\/jbmr.2210","volume":"29","author":"RJ Fajardo","year":"2014","unstructured":"Fajardo RJ, Karim L, Calley VI, Bouxsein ML (2014) A review of rodent models of type 2 diabetic skeletal fragility. J Bone Miner Res 29:1025\u20131040. https:\/\/doi.org\/10.1002\/jbmr.2210","journal-title":"J Bone Miner Res"},{"key":"1107_CR14","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1016\/j.ejphar.2010.03.048","volume":"636","author":"Z Fatehi-Hassanabad","year":"2010","unstructured":"Fatehi-Hassanabad Z, Chan CB, Furman BL (2010) Reactive oxygen species and endothelial function in diabetes. Eur J Pharmacol 636:8\u201317. https:\/\/doi.org\/10.1016\/j.ejphar.2010.03.048","journal-title":"Eur J Pharmacol"},{"key":"1107_CR15","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.832185","volume":"13","author":"G Fruhbeck","year":"2022","unstructured":"Fruhbeck G, Gomez-Ambrosi J, Ramirez B, Mentxaka A, Rodriguez A, Becerril S, Reina G, Valenti V, Moncada R, Silva C, Catalan V (2022) Increased levels of interleukin-36 in obesity and type 2 diabetes fuel adipose tissue inflammation by inducing its own expression and release by adipocytes and macrophages. Front Immunol 13:832185. https:\/\/doi.org\/10.3389\/fimmu.2022.832185","journal-title":"Front Immunol"},{"key":"1107_CR16","doi-asserted-by":"publisher","first-page":"H500","DOI":"10.1152\/ajpheart.00381.2014","volume":"308","author":"L Ge","year":"2015","unstructured":"Ge L, Zhou X, Ji WJ, Lu RY, Zhang Y, Zhang YD, Ma YQ, Zhao JH, Li YM (2015) Neutrophil extracellular traps in ischemia-reperfusion injury-induced myocardial no-reflow: therapeutic potential of DNase-based reperfusion strategy. Am J Physiol Heart Circ Physiol 308:H500-509. https:\/\/doi.org\/10.1152\/ajpheart.00381.2014","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"1107_CR17","doi-asserted-by":"publisher","first-page":"364","DOI":"10.1111\/dom.12827","volume":"19","author":"NN Gholap","year":"2017","unstructured":"Gholap NN, Achana FA, Davies MJ, Ray KK, Gray L, Khunti K (2017) Long-term mortality after acute myocardial infarction among individuals with and without diabetes: a systematic review and meta-analysis of studies in the post-reperfusion era. Diabetes Obes Metab 19:364\u2013374. https:\/\/doi.org\/10.1111\/dom.12827","journal-title":"Diabetes Obes Metab"},{"key":"1107_CR18","doi-asserted-by":"publisher","first-page":"458","DOI":"10.1016\/j.smim.2013.11.003","volume":"25","author":"MS Gresnigt","year":"2013","unstructured":"Gresnigt MS, van de Veerdonk FL (2013) Biology of IL-36 cytokines and their role in disease. Semin Immunol 25:458\u2013465. https:\/\/doi.org\/10.1016\/j.smim.2013.11.003","journal-title":"Semin Immunol"},{"key":"1107_CR19","doi-asserted-by":"publisher","first-page":"7816491","DOI":"10.1155\/2019\/7816491","volume":"2019","author":"R Helseth","year":"2019","unstructured":"Helseth R, Shetelig C, Andersen GO, Langseth MS, Limalanathan S, Opstad TB, Arnesen H, Hoffmann P, Eritsland J, Seljeflot I (2019) Neutrophil extracellular trap components associate with infarct size, ventricular function, and clinical outcome in STEMI. Mediators Inflamm 2019:7816491. https:\/\/doi.org\/10.1155\/2019\/7816491","journal-title":"Mediators Inflamm"},{"key":"1107_CR20","doi-asserted-by":"publisher","first-page":"421","DOI":"10.2337\/dc08-1161","volume":"32","author":"C Herder","year":"2009","unstructured":"Herder C, Brunner EJ, Rathmann W, Strassburger K, Tabak AG, Schloot NC, Witte DR (2009) Elevated levels of the anti-inflammatory interleukin-1 receptor antagonist precede the onset of type 2 diabetes: the Whitehall II study. Diabetes Care 32:421\u2013423. https:\/\/doi.org\/10.2337\/dc08-1161","journal-title":"Diabetes Care"},{"key":"1107_CR21","doi-asserted-by":"publisher","first-page":"773","DOI":"10.1038\/s41569-020-0403-y","volume":"17","author":"G Heusch","year":"2020","unstructured":"Heusch G (2020) Myocardial ischaemia-reperfusion injury and cardioprotection in perspective. Nat Rev Cardiol 17:773\u2013789. https:\/\/doi.org\/10.1038\/s41569-020-0403-y","journal-title":"Nat Rev Cardiol"},{"key":"1107_CR22","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1016\/j.medj.2023.12.007","volume":"5","author":"G Heusch","year":"2024","unstructured":"Heusch G (2024) Myocardial ischemia\/reperfusion: translational pathophysiology of ischemic heart disease. Med 5:10\u201331. https:\/\/doi.org\/10.1016\/j.medj.2023.12.007","journal-title":"Med"},{"key":"1107_CR23","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0060827","volume":"8","author":"ZG Huang","year":"2013","unstructured":"Huang ZG, Jin Q, Fan M, Cong XL, Han SF, Gao H, Shan Y (2013) Myocardial remodeling in diabetic cardiomyopathy associated with cardiac mast cell activation. PLoS ONE 8:e60827. https:\/\/doi.org\/10.1371\/journal.pone.0060827","journal-title":"PLoS ONE"},{"key":"1107_CR24","doi-asserted-by":"publisher","DOI":"10.3390\/cells10113000","author":"M Iwaszko","year":"2021","unstructured":"Iwaszko M, Bialy S, Bogunia-Kubik K (2021) Significance of interleukin (IL)-4 and IL-13 in inflammatory arthritis. Cells. https:\/\/doi.org\/10.3390\/cells10113000","journal-title":"Cells"},{"key":"1107_CR25","first-page":"405","volume-title":"Vitamins & hormones","author":"DR Johnson","year":"2006","unstructured":"Johnson DR, O\u2019Connor JC, Satpathy A, Freund GG (2006) Cytokines in type 2 diabetes. Vitamins & hormones. Academic Press, New York, pp 405\u2013441"},{"key":"1107_CR26","doi-asserted-by":"publisher","DOI":"10.1155\/2011\/742719","volume":"2011","author":"N Kakouros","year":"2011","unstructured":"Kakouros N, Rade JJ, Kourliouros A, Resar JR (2011) Platelet function in patients with diabetes mellitus: from a theoretical to a practical perspective. Int J Endocrinol 2011:742719. https:\/\/doi.org\/10.1155\/2011\/742719","journal-title":"Int J Endocrinol"},{"key":"1107_CR27","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0213162","volume":"14","author":"DPJ Kavanagh","year":"2019","unstructured":"Kavanagh DPJ, Gallagher MT, Kalia N (2019) Tify: A quality-based frame selection tool for improving the output of unstable biomedical imaging. PLoS ONE 14:e0213162. https:\/\/doi.org\/10.1371\/journal.pone.0213162","journal-title":"PLoS ONE"},{"key":"1107_CR28","doi-asserted-by":"publisher","first-page":"1918","DOI":"10.1093\/cvr\/cvz118","volume":"115","author":"DPJ Kavanagh","year":"2019","unstructured":"Kavanagh DPJ, Lokman AB, Neag G, Colley A, Kalia N (2019) Imaging the injured beating heart intravitally and the vasculoprotection afforded by haematopoietic stem cells. Cardiovasc Res 115:1918\u20131932. https:\/\/doi.org\/10.1093\/cvr\/cvz118","journal-title":"Cardiovasc Res"},{"key":"1107_CR29","doi-asserted-by":"publisher","first-page":"1901","DOI":"10.1177\/0300060516675504","volume":"45","author":"A Kibel","year":"2017","unstructured":"Kibel A, Selthofer-Relatic K, Drenjancevic I, Bacun T, Bosnjak I, Kibel D, Gros M (2017) Coronary microvascular dysfunction in diabetes mellitus. J Int Med Res 45:1901\u20131929. https:\/\/doi.org\/10.1177\/0300060516675504","journal-title":"J Int Med Res"},{"key":"1107_CR30","doi-asserted-by":"publisher","first-page":"123","DOI":"10.7570\/jomes22001","volume":"31","author":"JH Ko","year":"2022","unstructured":"Ko JH, Kim TN (2022) Type 2 diabetes remission with significant weight loss: definition and evidence-based interventions. J Obes Metab Syndr 31:123\u2013133. https:\/\/doi.org\/10.7570\/jomes22001","journal-title":"J Obes Metab Syndr"},{"key":"1107_CR31","doi-asserted-by":"publisher","first-page":"1053","DOI":"10.1136\/gutjnl-2019-318264","volume":"69","author":"PJ Koelink","year":"2020","unstructured":"Koelink PJ, Bloemendaal FM, Li B, Westera L, Vogels EWM, van Roest M, Gloudemans AK, van\u2019t Wout AB, Korf H, Vermeire S, Te Velde AA, Ponsioen CY, D\u2019Haens GR, Verbeek JS, Geiger TL, Wildenberg ME, van den Brink GR (2020) Anti-TNF therapy in IBD exerts its therapeutic effect through macrophage IL-10 signalling. Gut 69:1053\u20131063. https:\/\/doi.org\/10.1136\/gutjnl-2019-318264","journal-title":"Gut"},{"key":"1107_CR32","doi-asserted-by":"publisher","first-page":"6673","DOI":"10.1038\/ncomms7673","volume":"6","author":"E Kolaczkowska","year":"2015","unstructured":"Kolaczkowska E, Jenne CN, Surewaard BGJ, Thanabalasuriar A, Lee WY, Sanz MJ, Mowen K, Opdenakker G, Kubes P (2015) Molecular mechanisms of NET formation and degradation revealed by intravital imaging in the liver vasculature. Nat Commun 6:6673","journal-title":"Nat Commun"},{"key":"1107_CR33","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/918267","volume":"2012","author":"GK Kolluru","year":"2012","unstructured":"Kolluru GK, Bir SC, Kevil CG (2012) Endothelial dysfunction and diabetes: effects on angiogenesis, vascular remodeling, and wound healing. Int J Vasc Med 2012:918267. https:\/\/doi.org\/10.1155\/2012\/918267","journal-title":"Int J Vasc Med"},{"key":"1107_CR34","doi-asserted-by":"publisher","first-page":"2467","DOI":"10.1016\/j.jcin.2018.09.033","volume":"11","author":"M Konigstein","year":"2018","unstructured":"Konigstein M, Ben-Yehuda O, Smits PC, Love MP, Banai S, Perlman GY, Golomb M, Ozan MO, Liu M, Leon MB, Stone GW, Kandzari DE (2018) Outcomes among diabetic patients undergoing percutaneous coronary intervention with contemporary drug-eluting stents: analysis from the BIONICS randomized trial. JACC Cardiovasc Interv 11:2467\u20132476. https:\/\/doi.org\/10.1016\/j.jcin.2018.09.033","journal-title":"JACC Cardiovasc Interv"},{"key":"1107_CR35","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1189\/jlb.0302126","volume":"73","author":"KY Larbi","year":"2003","unstructured":"Larbi KY, Dangerfield JP, Culley FJ, Marshall D, Haskard DO, Jose PJ, Williams TJ, Nourshargh S (2003) P-selectin mediates IL-13-induced eosinophil transmigration but not eotaxin generation in vivo: a comparative study with IL-4-elicited responses. J Leukoc Biol 73:65\u201373. https:\/\/doi.org\/10.1189\/jlb.0302126","journal-title":"J Leukoc Biol"},{"key":"1107_CR36","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/j.yjmcc.2015.12.020","volume":"91","author":"A Lejay","year":"2016","unstructured":"Lejay A, Fang F, John R, Van JA, Barr M, Thaveau F, Chakfe N, Geny B, Scholey JW (2016) Ischemia reperfusion injury, ischemic conditioning and diabetes mellitus. J Mol Cell Cardiol 91:11\u201322. https:\/\/doi.org\/10.1016\/j.yjmcc.2015.12.020","journal-title":"J Mol Cell Cardiol"},{"key":"1107_CR37","doi-asserted-by":"publisher","first-page":"e23611","DOI":"10.1002\/jcla.23611","volume":"35","author":"Y Li","year":"2021","unstructured":"Li Y, Chen SS, Zhao TQ, Li MC (2021) Serum IL-36 cytokines levels in type 2 diabetes mellitus patients and their association with obesity, insulin resistance, and inflammation. J Clin Lab Anal 35:e23611. https:\/\/doi.org\/10.1002\/jcla.23611","journal-title":"J Clin Lab Anal"},{"key":"1107_CR38","doi-asserted-by":"publisher","first-page":"1090","DOI":"10.1159\/000366323","volume":"34","author":"B Littlejohns","year":"2014","unstructured":"Littlejohns B, Lin H, Angelini GD, Halestrap AP, Suleiman MS (2014) Switching back to normal diet following high-fat diet feeding reduces cardiac vulnerability to ischaemia and reperfusion injury. Cell Physiol Biochem 34:1090\u20131100. https:\/\/doi.org\/10.1159\/000366323","journal-title":"Cell Physiol Biochem"},{"key":"1107_CR39","doi-asserted-by":"publisher","first-page":"1019","DOI":"10.1126\/sciadv.adj1019","volume":"9","author":"C Liu","year":"2023","unstructured":"Liu C, Yalavarthi S, Tambralli A, Zeng L, Rysenga CE, Alizadeh N, Hudgins L, Liang W, NaveenKumar SK, Shi H, Shelef MA, Atkins KB, Pennathur S, Knight JS (2023) Inhibition of neutrophil extracellular trap formation alleviates vascular dysfunction in type 1 diabetic mice. Sci Adv 9:1019. https:\/\/doi.org\/10.1126\/sciadv.adj1019","journal-title":"Sci Adv"},{"key":"1107_CR40","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2020.106264","volume":"82","author":"Y Liu","year":"2020","unstructured":"Liu Y, Chen T, Zhou F, Mu D, Liu S (2020) Interleukin-38 increases the insulin sensitivity in children with the type 2 diabetes. Int Immunopharmacol 82:106264. https:\/\/doi.org\/10.1016\/j.intimp.2020.106264","journal-title":"Int Immunopharmacol"},{"key":"1107_CR41","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1038\/nmeth.1543","volume":"8","author":"MR Looney","year":"2011","unstructured":"Looney MR, Thornton EE, Sen D, Lamm WJ, Glenny RW, Krummel MF (2011) Stabilized imaging of immune surveillance in the mouse lung. Nat Methods 8:91\u201396. https:\/\/doi.org\/10.1038\/nmeth.1543","journal-title":"Nat Methods"},{"key":"1107_CR42","doi-asserted-by":"publisher","first-page":"1655","DOI":"10.1161\/01.CIR.0000089189.70578.E2","volume":"108","author":"TF Luscher","year":"2003","unstructured":"Luscher TF, Creager MA, Beckman JA, Cosentino F (2003) Diabetes and vascular disease: pathophysiology, clinical consequences, and medical therapy: part II. Circulation 108:1655\u20131661. https:\/\/doi.org\/10.1161\/01.CIR.0000089189.70578.E2","journal-title":"Circulation"},{"key":"1107_CR43","doi-asserted-by":"publisher","first-page":"1182","DOI":"10.1161\/CIRCRESAHA.116.304944","volume":"116","author":"A Mangold","year":"2015","unstructured":"Mangold A, Alias S, Scherz T, Hofbauer M, Jakowitsch J, Panzenbock A, Simon D, Laimer D, Bangert C, Kammerlander A, Mascherbauer J, Winter MP, Distelmaier K, Adlbrecht C, Preissner KT, Lang IM (2015) Coronary neutrophil extracellular trap burden and deoxyribonuclease activity in ST-elevation acute coronary syndrome are predictors of ST-segment resolution and infarct size. Circ Res 116:1182\u20131192. https:\/\/doi.org\/10.1161\/CIRCRESAHA.116.304944","journal-title":"Circ Res"},{"key":"1107_CR44","doi-asserted-by":"publisher","first-page":"2599","DOI":"10.1111\/febs.13775","volume":"283","author":"SJ Martin","year":"2016","unstructured":"Martin SJ (2016) Cell death and inflammation: the case for IL-1 family cytokines as the canonical DAMPs of the immune system. FEBS J 283:2599\u20132615. https:\/\/doi.org\/10.1111\/febs.13775","journal-title":"FEBS J"},{"key":"1107_CR45","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1042\/cs0870031","volume":"87","author":"PG McNally","year":"1994","unstructured":"McNally PG, Watt PAC, Rimmer T, Burden AC, Hearnshaw JR, Thurston H (1994) Impaired contraction and endothelium-dependent relaxation in isolated resistance vessels from patients with insulin-dependent diabetes mellitus. Clin Sci 87:31\u201336. https:\/\/doi.org\/10.1042\/cs0870031","journal-title":"Clin Sci"},{"key":"1107_CR46","doi-asserted-by":"publisher","DOI":"10.3390\/jcm12041602","author":"D Milasinovic","year":"2023","unstructured":"Milasinovic D, Nedeljkovic O, Maksimovic R, Sobic-Saranovic D, Dukic D, Zobenica V, Jelic D, Zivkovic M, Dedovic V, Stankovic S, Asanin M, Vukcevic V (2023) Coronary microcirculation: the next frontier in the management of STEMI. J Clin Med. https:\/\/doi.org\/10.3390\/jcm12041602","journal-title":"J Clin Med"},{"key":"1107_CR47","doi-asserted-by":"publisher","DOI":"10.3390\/cells9092130","author":"SR Mulay","year":"2020","unstructured":"Mulay SR, Anders HJ (2020) Neutrophils and neutrophil extracellular traps regulate immune responses in health and disease. Cells. https:\/\/doi.org\/10.3390\/cells9092130","journal-title":"Cells"},{"key":"1107_CR48","doi-asserted-by":"publisher","first-page":"H1049","DOI":"10.1152\/ajpheart.2000.278.4.H1049","volume":"278","author":"TO Nossuli","year":"2000","unstructured":"Nossuli TO, Lakshminarayanan V, Baumgarten G, Taffet GE, Ballantyne CM, Michael LH, Entman ML (2000) A chronic mouse model of myocardial ischemia-reperfusion: essential in cytokine studies. Am J Physiol Heart Circ Physiol 278:H1049-1055. https:\/\/doi.org\/10.1152\/ajpheart.2000.278.4.H1049","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"1107_CR49","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.624184","volume":"9","author":"L Pezhman","year":"2021","unstructured":"Pezhman L, Tahrani A, Chimen M (2021) Dysregulation of leukocyte trafficking in type 2 diabetes: mechanisms and potential therapeutic avenues. Front Cell Dev Biol 9:624184. https:\/\/doi.org\/10.3389\/fcell.2021.624184","journal-title":"Front Cell Dev Biol"},{"key":"1107_CR50","doi-asserted-by":"publisher","first-page":"1272","DOI":"10.21037\/atm-20-6737","volume":"9","author":"J Quiroz","year":"2021","unstructured":"Quiroz J, Yazdanyar A (2021) Animal models of diabetic retinopathy. Ann Transl Med 9:1272. https:\/\/doi.org\/10.21037\/atm-20-6737","journal-title":"Ann Transl Med"},{"key":"1107_CR51","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1186\/s12933-019-0870-9","volume":"18","author":"SN Randeria","year":"2019","unstructured":"Randeria SN, Thomson GJA, Nell TA, Roberts T, Pretorius E (2019) Inflammatory cytokines in type 2 diabetes mellitus as facilitators of hypercoagulation and abnormal clot formation. Cardiovasc Diabetol 18:72. https:\/\/doi.org\/10.1186\/s12933-019-0870-9","journal-title":"Cardiovasc Diabetol"},{"key":"1107_CR52","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1161\/CIRCRESAHA.115.306656","volume":"118","author":"PM Ridker","year":"2016","unstructured":"Ridker PM (2016) From C-reactive protein to interleukin-6 to interleukin-1: moving upstream to identify novel targets for atheroprotection. Circ Res 118:145\u2013156. https:\/\/doi.org\/10.1161\/CIRCRESAHA.115.306656","journal-title":"Circ Res"},{"key":"1107_CR53","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s00109-020-01988-7","volume":"99","author":"A Salminen","year":"2021","unstructured":"Salminen A (2021) Increased immunosuppression impairs tissue homeostasis with aging and age-related diseases. J Mol Med (Berl) 99:1\u201320. https:\/\/doi.org\/10.1007\/s00109-020-01988-7","journal-title":"J Mol Med (Berl)"},{"key":"1107_CR54","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.48704","volume":"15","author":"P Sharma","year":"2023","unstructured":"Sharma P, Chakole S (2023) Unlocking the potential of type 2 diabetes mellitus remission. Cureus 15:e48704. https:\/\/doi.org\/10.7759\/cureus.48704","journal-title":"Cureus"},{"key":"1107_CR55","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1186\/s12933-018-0703-2","volume":"17","author":"WD Strain","year":"2018","unstructured":"Strain WD, Paldanius PM (2018) Diabetes, cardiovascular disease and the microcirculation. Cardiovasc Diabetol 17:57. https:\/\/doi.org\/10.1186\/s12933-018-0703-2","journal-title":"Cardiovasc Diabetol"},{"key":"1107_CR56","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2021.628843","volume":"8","author":"AR Sun","year":"2021","unstructured":"Sun AR, Wu X, Crawford R, Li H, Mei L, Luo Y, Xiao Y, Mao X, Prasadam I (2021) Effects of diet induced weight reduction on cartilage pathology and inflammatory mediators in the joint tissues. Front Med (Lausanne) 8:628843. https:\/\/doi.org\/10.3389\/fmed.2021.628843","journal-title":"Front Med (Lausanne)"},{"key":"1107_CR57","doi-asserted-by":"publisher","first-page":"50","DOI":"10.15420\/ecr.2018.33.1","volume":"14","author":"S Tsalamandris","year":"2019","unstructured":"Tsalamandris S, Antonopoulos AS, Oikonomou E, Papamikroulis GA, Vogiatzi G, Papaioannou S, Deftereos S, Tousoulis D (2019) The role of inflammation in diabetes: current concepts and future perspectives. Eur Cardiol 14:50\u201359. https:\/\/doi.org\/10.15420\/ecr.2018.33.1","journal-title":"Eur Cardiol"},{"key":"1107_CR58","doi-asserted-by":"publisher","first-page":"869","DOI":"10.1007\/s00395-024-01055-z","volume":"119","author":"RWA van Drie","year":"2024","unstructured":"van Drie RWA, van de Wouw J, Zandbergen LM, Dehairs J, Swinnen JV, Mulder MT, Verhaar MC, MaassenVanDenBrink A, Duncker DJ, Sorop O, Merkus D (2024) Vasodilator reactive oxygen species ameliorate perturbed myocardial oxygen delivery in exercising swine with multiple comorbidities. Basic Res Cardiol 119:869\u2013887. https:\/\/doi.org\/10.1007\/s00395-024-01055-z","journal-title":"Basic Res Cardiol"},{"key":"1107_CR59","doi-asserted-by":"publisher","first-page":"419","DOI":"10.5114\/ceji.2021.111493","volume":"46","author":"H Wadehn","year":"2021","unstructured":"Wadehn H, Raluy LP, Kolman J, Duecker C, Trochimiuk M, Appl B, Boettcher M, Reinshagen K, Trah J (2021) Time- and dose-dependent inhibition of neutrophil extracellular trap formation by blocking of the interleukin-1 receptor. Cent Eur J Immunol 46:419\u2013426. https:\/\/doi.org\/10.5114\/ceji.2021.111493","journal-title":"Cent Eur J Immunol"},{"key":"1107_CR60","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1016\/j.bbrc.2022.02.088","volume":"605","author":"DW Williams","year":"2022","unstructured":"Williams DW, Kim RH (2022) Epithelial cells release IL-36alpha in extracellular vesicles following mechanical damage. Biochem Biophys Res Commun 605:56\u201362. https:\/\/doi.org\/10.1016\/j.bbrc.2022.02.088","journal-title":"Biochem Biophys Res Commun"},{"key":"1107_CR61","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1016\/j.bbrc.2018.11.114","volume":"508","author":"K Xu","year":"2019","unstructured":"Xu K, Sun J, Chen S, Li Y, Peng X, Li M, Li Y (2019) Hydrodynamic delivery of IL-38 gene alleviates obesity-induced inflammation and insulin resistance. Biochem Biophys Res Commun 508:198\u2013202. https:\/\/doi.org\/10.1016\/j.bbrc.2018.11.114","journal-title":"Biochem Biophys Res Commun"},{"key":"1107_CR62","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1016\/0002-9343(86)90719-9","volume":"80","author":"R Zatz","year":"1986","unstructured":"Zatz R, Brenner BM (1986) Pathogenesis of diabetic microangiopathy. The hemodynamic view. Am J Med 80:443\u2013453. https:\/\/doi.org\/10.1016\/0002-9343(86)90719-9","journal-title":"Am J Med"},{"key":"1107_CR63","doi-asserted-by":"publisher","first-page":"1022380","DOI":"10.3389\/fimmu.2022.1022380","volume":"13","author":"F Zhang","year":"2022","unstructured":"Zhang F, Li Y, Wu J, Zhang J, Cao P, Sun Z, Wang W (2022) The role of extracellular traps in ischemia reperfusion injury. Front Immunol 13:1022380. https:\/\/doi.org\/10.3389\/fimmu.2022.1022380","journal-title":"Front Immunol"},{"key":"1107_CR64","doi-asserted-by":"publisher","first-page":"7319277","DOI":"10.1155\/2022\/7319277","volume":"2022","author":"SR Zhao","year":"2022","unstructured":"Zhao SR, Huang R, Liu F, Li Y, Gong Y, Xing J (2022) Study on correlation between type 2 diabetes and no-reflow after PCI. Dis Markers 2022:7319277. https:\/\/doi.org\/10.1155\/2022\/7319277","journal-title":"Dis Markers"}],"container-title":["Basic Research in Cardiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00395-025-01107-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00395-025-01107-y\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00395-025-01107-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,11]],"date-time":"2025-06-11T12:46:53Z","timestamp":1749646013000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00395-025-01107-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,17]]},"references-count":64,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2025,6]]}},"alternative-id":["1107"],"URL":"https:\/\/doi.org\/10.1007\/s00395-025-01107-y","relation":{},"ISSN":["1435-1803"],"issn-type":[{"value":"1435-1803","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,17]]},"assertion":[{"value":"6 December 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 April 2025","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 April 2025","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 April 2025","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors confirm they have no conflicts of interest to disclose. DJH receives licensing revenue from Celtarys Research and has filed patents on diabetes drug therapy.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"Murine experiments were conducted in accordance with the Animals (Scientific Procedures) Act of 1986 (Project licence P552D4447).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}}]}}