{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T12:40:24Z","timestamp":1767789624948,"version":"3.49.0"},"reference-count":32,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T00:00:00Z","timestamp":1767744000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cardiovasc. Med."],"abstract":"<jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>\n                      Cardiovascular disease remains the leading cause of death after kidney transplantation. Coronary microvascular dysfunction (CMD) is common in kidney transplant recipients (KTRs), prognostically informative for cardiovascular events, and tightly related to inflammation. We aimed to test whether pretransplant monocytic expression of pyroptosis-related genes (\n                      <jats:italic>IL-1\u03b2<\/jats:italic>\n                      ,\n                      <jats:italic>GSDMD<\/jats:italic>\n                      ,\n                      <jats:italic>Caspase-1<\/jats:italic>\n                      , and\n                      <jats:italic>NLRP3<\/jats:italic>\n                      ) independently predicts long-term mortality and major adverse cardiovascular events (MACE) in KTRs, and to evaluate its associations with CMD.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We enrolled 305 KTRs. Monocytes were isolated preoperatively and qPCR quantified the four genes (normalized to GAPDH). MACE included death, myocardial infarction, stroke, and heart failure. Multivariable Cox regression was used to adjust for confounders associated with prognosis. CMD was evaluated using coronary flow reserve (CFR) in 41 KTRs and serum syndecan-1 levels (an endothelial injury marker) in 88 KTRs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Over a median 4.0 years, 62\/305 (20.3%) had MACE.\n                      <jats:italic>IL-1\u03b2<\/jats:italic>\n                      expression was higher in those with events. In Cox models with\n                      <jats:italic>IL-1\u03b2<\/jats:italic>\n                      entered as a standardized continuous variable (per SD),\n                      <jats:italic>IL-1\u03b2<\/jats:italic>\n                      independently predicted death (adjusted HR 1.530, 95%CI 1.165\u20132.009) and MACE (adjusted HR 1.622, 95%CI 1.283\u20132.052). When modeled categorically as tertiles, the highest vs. lowest\n                      <jats:italic>IL-1\u03b2<\/jats:italic>\n                      tertile conferred greater risk (death, adjusted HR 3.771, 95%CI 1.516\u20139.384; MACE, adjusted HR 4.398, 95%CI 2.003\u20139.654).\n                      <jats:italic>IL-1\u03b2<\/jats:italic>\n                      correlated inversely with CFR (R\u2009=\u2009\u22120.40,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.009) and positively with syndecan-1 (R\u2009=\u20090.47,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&amp;lt;\u20090.001). Other genes showed weaker or nonsignificant associations.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      <jats:italic>IL-1\u03b2<\/jats:italic>\n                      is a robust, independent predictor of death and MACE in KTRs. Its associations with impaired CFR and elevated syndecan-1 support a mechanistic link to CMD.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcvm.2025.1689566","type":"journal-article","created":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T07:09:25Z","timestamp":1767769765000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Monocyte IL-1\u03b2 predicts adverse cardiovascular events and associates with coronary microvascular dysfunction in kidney transplant recipients"],"prefix":"10.3389","volume":"12","author":[{"given":"Zhengwei","family":"Yin","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qingyan","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianle","family":"Han","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junwei","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tao","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingjun","family":"Suo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuaiping","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaobo","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuailin","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chang\u2019an","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,1,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"876","DOI":"10.1016\/j.kint.2022.05.017","article-title":"A population cohort analysis of English transplant centers indicates major adverse cardiovascular events after kidney transplantation","volume":"102","author":"Anderson","year":"2022","journal-title":"Kidney Int"},{"key":"B2","doi-asserted-by":"publisher","first-page":"355","DOI":"10.2215\/CJN.0000000000000360","article-title":"Trends and specific causes of cardiovascular mortality after kidney transplantation in Finland","volume":"19","author":"Helve","year":"2024","journal-title":"Clin J Am Soc Nephrol"},{"key":"B3","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1093\/ckj\/sfab216","article-title":"Plasma biomarkers outperform echocardiographic measurements for cardiovascular risk prediction in kidney transplant recipients: results of the HOME ALONE study","volume":"15","author":"Emrich","year":"2022","journal-title":"Clin Kidney J"},{"key":"B4","doi-asserted-by":"publisher","first-page":"2307","DOI":"10.1016\/j.ekir.2023.08.021","article-title":"Triglyceride-glucose index and cardiovascular events in kidney transplant recipients","volume":"8","author":"Colladant","year":"2023","journal-title":"Kidney Int Rep"},{"key":"B5","doi-asserted-by":"publisher","first-page":"e034108","DOI":"10.1161\/JAHA.124.034108","article-title":"Visit-to-visit systolic blood pressure variability independently predicts cardiovascular events in a kidney transplant recipients\u2019 cohort","volume":"13","author":"Bussalino","year":"2024","journal-title":"J Am Heart Assoc"},{"key":"B6","doi-asserted-by":"publisher","first-page":"e015858","DOI":"10.1161\/CIRCIMAGING.123.015858","article-title":"Comparative effectiveness of PET and SPECT MPI for predicting cardiovascular events after kidney transplant","volume":"17","author":"Huck","year":"2024","journal-title":"Circ Cardiovasc Imaging"},{"key":"B7","doi-asserted-by":"publisher","first-page":"1322176","DOI":"10.3389\/fcvm.2024.1322176","article-title":"Standardized risk-stratified cardiac assessment and early post-transplant cardiovascular complications in kidney transplant recipients","volume":"11","author":"Rajnochova Bloudickova","year":"2024","journal-title":"Front Cardiovasc Med"},{"key":"B8","doi-asserted-by":"publisher","first-page":"2625","DOI":"10.1016\/j.jacc.2018.09.042","article-title":"Coronary microvascular disease pathogenic mechanisms and therapeutic options: JACC state-of-the-art review","volume":"72","author":"Taqueti","year":"2018","journal-title":"J Am Coll Cardiol"},{"key":"B9","doi-asserted-by":"publisher","first-page":"1686","DOI":"10.1016\/j.jcmg.2018.08.018","article-title":"Global coronary flow reserve measured during stress cardiac magnetic resonance imaging is an independent predictor of adverse cardiovascular events","volume":"12","author":"Indorkar","year":"2019","journal-title":"JACC Cardiovasc Imaging"},{"key":"B10","doi-asserted-by":"publisher","first-page":"856","DOI":"10.1093\/cvr\/cvaa006","article-title":"Treatment of coronary microvascular dysfunction","volume":"116","author":"Bairey Merz","year":"2020","journal-title":"Cardiovasc Res"},{"key":"B11","doi-asserted-by":"publisher","first-page":"300","DOI":"10.1186\/s12933-024-02400-1","article-title":"Combined risk estimates of diabetes and coronary angiography-derived index of microcirculatory resistance in patients with non-ST elevation myocardial infarction","volume":"23","author":"Chen","year":"2024","journal-title":"Cardiovasc Diabetol"},{"key":"B12","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1016\/j.jcmg.2023.07.014","article-title":"Body composition, coronary microvascular dysfunction, and future risk of cardiovascular events including heart failure","volume":"17","author":"Souza","year":"2024","journal-title":"JACC Cardiovasc Imaging"},{"key":"B13","doi-asserted-by":"publisher","first-page":"1075","DOI":"10.1161\/CIRCULATIONAHA.123.067083","article-title":"Relationship of subendocardial perfusion to myocardial injury, cardiac structure, and clinical outcomes among patients with hypertension","volume":"150","author":"Xu","year":"2024","journal-title":"Circulation"},{"key":"B14","doi-asserted-by":"publisher","first-page":"728","DOI":"10.1038\/s41569-025-01163-w","article-title":"Vascular (dys)function in the failing heart","volume":"22","author":"Liberale","year":"2025","journal-title":"Nat Rev Cardiol"},{"key":"B15","doi-asserted-by":"publisher","first-page":"1112","DOI":"10.1093\/eurheartj\/ehae827","article-title":"Skeletal muscle adiposity, coronary microvascular dysfunction, and adverse cardiovascular outcomes","volume":"46","author":"Souza","year":"2025","journal-title":"Eur Heart J"},{"key":"B16","doi-asserted-by":"publisher","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":"B17","doi-asserted-by":"publisher","first-page":"536","DOI":"10.1111\/echo.14625","article-title":"Impaired coronary microcirculation is associated with left ventricular diastolic dysfunction in end-stage chronic kidney disease patients","volume":"37","author":"Papamichail","year":"2020","journal-title":"Echocardiography"},{"key":"B18","doi-asserted-by":"publisher","first-page":"600","DOI":"10.1111\/echo.15598","article-title":"Coronary microcirculation and left ventricular diastolic function but not myocardial deformation indices are impaired early in patients with chronic kidney disease","volume":"40","author":"Lakkas","year":"2023","journal-title":"Echocardiography"},{"key":"B19","doi-asserted-by":"publisher","first-page":"1489403","DOI":"10.3389\/fcvm.2024.1489403","article-title":"Prognostic impact of coronary microvascular dysfunction assessed by AMR in acute coronary syndrome patients with chronic kidney disease","volume":"11","author":"Guo","year":"2024","journal-title":"Front Cardiovasc Med"},{"key":"B20","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1016\/j.carrev.2024.12.009","article-title":"Functional coronary microvascular dysfunction among patients with chronic kidney disease","volume":"71","author":"Chitturi","year":"2025","journal-title":"Cardiovasc Revasc Med"},{"key":"B21","doi-asserted-by":"publisher","first-page":"e029341","DOI":"10.1161\/JAHA.122.029341","article-title":"Circulating biomarkers in coronary microvascular dysfunction","volume":"12","author":"Chakrala","year":"2023","journal-title":"J Am Heart Assoc"},{"key":"B22","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1016\/j.jacbts.2022.08.009","article-title":"Coronary flow reserve, inflammation, and myocardial strain: the CIRT-CFR trial","volume":"8","author":"Taqueti","year":"2023","journal-title":"JACC Basic Transl Sci"},{"key":"B23","doi-asserted-by":"publisher","first-page":"e014940","DOI":"10.1161\/CIRCIMAGING.122.014940","article-title":"Association between systemic vasculitis and coronary microvascular dysfunction in the absence of obstructive coronary artery disease","volume":"16","author":"Weber","year":"2023","journal-title":"Circ Cardiovasc Imaging"},{"key":"B24","doi-asserted-by":"publisher","first-page":"997","DOI":"10.1161\/ATVBAHA.123.320471","article-title":"Coronary microvascular dysfunction is associated with a proinflammatory circulating transcriptome in patients with nonobstructive coronary arteries","volume":"44","author":"Smilowitz","year":"2024","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"B25","doi-asserted-by":"publisher","first-page":"2891","DOI":"10.7150\/ijbs.107965","article-title":"De-succinylation-induced accumulation of TRMT10C in the nucleus plays a detrimental role in coronary microembolization via its m1A modification function","volume":"21","author":"Hu","year":"2025","journal-title":"Int J Biol Sci"},{"key":"B26","doi-asserted-by":"publisher","first-page":"643","DOI":"10.1093\/cvr\/cvae257","article-title":"SGLT2 expression in human vasculature and heart correlates with low-grade inflammation and causes eNOS-NO\/ROS imbalance","volume":"121","author":"Mroueh","year":"2025","journal-title":"Cardiovasc Res"},{"key":"B27","doi-asserted-by":"publisher","first-page":"2768","DOI":"10.1016\/j.apsb.2021.02.006","article-title":"Gasdermin D in pyroptosis","volume":"11","author":"Burdette","year":"2021","journal-title":"Acta Pharm Sin B"},{"key":"B28","doi-asserted-by":"publisher","first-page":"101809","DOI":"10.1016\/j.smim.2023.101809","article-title":"Pyroptosis in cardiovascular diseases: pumping gasdermin on the fire","volume":"69","author":"Yarovinsky","year":"2023","journal-title":"Semin Immunol"},{"key":"B29","doi-asserted-by":"publisher","first-page":"312","DOI":"10.1038\/s41569-023-00957-0","article-title":"Programmed death of macrophages in atherosclerosis: mechanisms and therapeutic targets","volume":"21","author":"De Meyer","year":"2024","journal-title":"Nat Rev Cardiol"},{"key":"B30","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1016\/j.cytogfr.2025.05.005","article-title":"The secretion of interleukin-1beta","volume":"84","author":"Ford","year":"2025","journal-title":"Cytokine Growth Factor Rev"},{"key":"B31","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1186\/s43556-025-00249-8","article-title":"GSDMD-mediated pyroptosis: molecular mechanisms, diseases and therapeutic targets","volume":"6","author":"Li","year":"2025","journal-title":"Mol Biomed"},{"key":"B32","doi-asserted-by":"publisher","first-page":"950102","DOI":"10.3389\/fcvm.2022.950102","article-title":"Association of endothelial glycocalyx shedding and coronary microcirculation assessed by an angiography-derived index of microcirculatory resistance in patients with suspected coronary artery disease","volume":"9","author":"Liu","year":"2022","journal-title":"Front Cardiovasc Med"}],"container-title":["Frontiers in Cardiovascular Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcvm.2025.1689566\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T07:09:27Z","timestamp":1767769767000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcvm.2025.1689566\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,7]]},"references-count":32,"alternative-id":["10.3389\/fcvm.2025.1689566"],"URL":"https:\/\/doi.org\/10.3389\/fcvm.2025.1689566","relation":{},"ISSN":["2297-055X"],"issn-type":[{"value":"2297-055X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,7]]},"article-number":"1689566"}}