{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T08:17:17Z","timestamp":1793089037378,"version":"4.5.0"},"reference-count":41,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,7,14]],"date-time":"2021-07-14T00:00:00Z","timestamp":1626220800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:p>Uraemic cardiomyopathy (UCM) is one of the most common complications in chronic kidney disease (CKD). Our aim was to compare characteristics of various UCM mouse models. Mice were assigned to the following groups: the pole ligation group, 5\/6 nephrectomy group (5\/6Nx), uninephrectomy plus contralateral ischemia followed by reperfusion group (IR), adenine group, and sham group. Mice were sacrificed at 4, 8, and 16 weeks after surgery in the pole ligation, 5\/6Nx, and IR groups, respectively. In the adenine group, mice were sacrificed at 16 weeks after the adenine diet. The structure and function of the heart and the expression of fibroblast growth factor 23 (FGF-23) and growth differentiation factor 15 (GDF-15) in hearts were assessed. The mortality in the 5\/6 Nx group was significantly higher than that in the pole ligation, IR, and adenine groups. Echocardiogram and histological examination showed cardiac hypertrophy in the adenine,5\/6Nx, ligation group, and IR group. In addition, cardiac fibrosis occurred in all CKD modeling groups. Interestingly, cardiac fibrosis was more serious in the IR and adenine groups. FGF-23 expression in sham mice was similar to that in modeling groups; however, the GDF-15 level was decreased in modeling groups. Our results suggest that the four models of UCM show different phenotypical features, molding time and mortality. GDF-15 expression in the hearts of UCM mice was downregulated compared with sham group mice.<\/jats:p>","DOI":"10.3389\/fmed.2021.690517","type":"journal-article","created":{"date-parts":[[2021,7,14]],"date-time":"2021-07-14T06:58:01Z","timestamp":1626245881000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":15,"title":["Uraemic Cardiomyopathy in Different Mouse Models"],"prefix":"10.3389","volume":"8","author":[{"given":"Cheng","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caidie","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanzhang","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingfeng","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huijuan","family":"Mao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changying","family":"Xing","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,7,14]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"2038","DOI":"10.1001\/jama.298.17.2038","article-title":"Prevalence of chronic kidney disease in the United States","volume":"298","author":"Coresh","year":"2007","journal-title":"Jama."},{"key":"B2","doi-asserted-by":"publisher","first-page":"566","DOI":"10.1038\/clpt.2009.137","article-title":"Public health consequences of chronic kidney disease","volume":"86","author":"Weiner","year":"2009","journal-title":"Clin Pharmacol Ther."},{"key":"B3","doi-asserted-by":"publisher","first-page":"e1","DOI":"10.1053\/j.ajkd.2011.11.015","article-title":"\u2018United States renal data system 2011 annual data report: atlas of chronic kidney disease & end-stage renal disease in the United States","volume":"59","author":"Collins","year":"2012","journal-title":"Am J Kidney Dis"},{"key":"B4","doi-asserted-by":"publisher","first-page":"1267","DOI":"10.1016\/S0272-6386(03)00359-7","article-title":"Heart failure as a cause for hospitalization in chronic dialysis patients","volume":"41","author":"Trespalacios","year":"2003","journal-title":"Am J Kidney Dis."},{"key":"B5","doi-asserted-by":"publisher","first-page":"F450","DOI":"10.1152\/ajprenal.00472.2007","article-title":"Partial nephrectomy as a model for uremic cardiomyopathy in the mouse","volume":"294","author":"Kennedy","year":"2008","journal-title":"Am J Physiol Renal Physiol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1097\/01.ASN.0000037403.95126.03","article-title":"Effect of chronic renal failure on cardiac contractile function, calcium cycling, and gene expression of proteins important for calcium homeostasis in the rat","volume":"14","author":"Kennedy","year":"2003","journal-title":"J Am Soc Nephrol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"488","DOI":"10.1161\/01.HYP.0000202594.82271.92","article-title":"Central role for the cardiotonic steroid marinobufagenin in the pathogenesis of experimental uremic cardiomyopathy","volume":"47","author":"Kennedy","year":"2006","journal-title":"Hypertension."},{"key":"B8","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1038\/hr.2009.25","article-title":"Angiotensin (1-7) prevent heart dysfunction and left ventricular remodeling caused by renal dysfunction in 5\/6 nephrectomy mice","volume":"32","author":"Li","year":"2009","journal-title":"Hypertens Res."},{"key":"B9","doi-asserted-by":"publisher","first-page":"8296","DOI":"10.1096\/fj.202000214RR","article-title":"Inhibition of urea transporter ameliorates uremic cardiomyopathy in chronic kidney disease","volume":"34","author":"Kuma","year":"2020","journal-title":"FASEB J."},{"key":"B10","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1016\/j.jacbts.2019.10.011","article-title":"Macrophage-derived exosomal mir-155 regulating cardiomyocyte pyroptosis and hypertrophy in uremic Cardiomyopathy","volume":"5","author":"Wang","year":"2020","journal-title":"JACC Basic Transl Sci."},{"key":"B11","doi-asserted-by":"publisher","first-page":"1104","DOI":"10.1016\/j.kint.2016.10.034","article-title":"Recombinant \u03b1-Klotho may be prophylactic and therapeutic for acute to chronic kidney disease progression and uremic cardiomyopathy","volume":"91","author":"Hu","year":"2017","journal-title":"Kidney Int."},{"key":"B12","doi-asserted-by":"publisher","first-page":"55825","DOI":"10.3791\/55825","article-title":"A mouse 5\/6th nephrectomy model that induces experimental uremic cardiomyopathy","volume":"129","author":"Wang","year":"2017","journal-title":"J Visualized Exp."},{"key":"B13","doi-asserted-by":"publisher","first-page":"346","DOI":"10.1186\/s12882-018-1155-3","article-title":"A novel model of reno-cardiac syndrome in the c57BL\/ 6 mouse strain","volume":"19","author":"Kieswich","year":"2018","journal-title":"BMC Nephrol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"2275","DOI":"10.1681\/ASN.2005121273","article-title":"International comparison of the relationship of chronic kidney disease prevalence and ESRD risk","volume":"17","author":"Hallan","year":"2006","journal-title":"J Am Soc Nephrol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"8","DOI":"10.2215\/CJN.00730805","article-title":"Kidney-heart interactions: epidemiology, pathogenesis, and treatment","volume":"1","author":"Berl","year":"2006","journal-title":"Clin J Am Soc Nephrol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"138","DOI":"10.1016\/j.kint.2018.07.028","article-title":"AT2 receptor stimulation inhibits phosphate-induced vascular calcification","volume":"95","author":"Kukida","year":"2019","journal-title":"Kidney Int."},{"key":"B17","doi-asserted-by":"publisher","first-page":"1302","DOI":"10.1038\/s41598-018-37690-5","article-title":"Chronic kidney disease induces left ventricular overexpression of the pro-hypertrophic microRNA-212","volume":"9","author":"S\u00e1rk\u00f6zy","year":"2019","journal-title":"Sci Rep."},{"key":"B18","doi-asserted-by":"publisher","first-page":"1140","DOI":"10.1093\/ndt\/gfs569","article-title":"Thalidomide suppresses inflammation in adenine-induced CKD with uraemia in mice","volume":"28","author":"Santana","year":"2013","journal-title":"Nephrol Dial Transplant."},{"key":"B19","doi-asserted-by":"publisher","first-page":"669","DOI":"10.1016\/j.kint.2017.02.023","article-title":"Klotho restoration via acetylation of peroxisome proliferation-activated receptor \u03b3 reduces the progression of chronic kidney disease","volume":"92","author":"Lin","year":"2017","journal-title":"Kidney Int."},{"key":"B20","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1016\/j.kint.2016.07.040","article-title":"Rhein reverses klotho repression via promoter demethylation and protects against kidney and bone injuries in mice with chronic kidney disease","volume":"91","author":"Zhang","year":"2017","journal-title":"Kidney Int."},{"key":"B21","doi-asserted-by":"publisher","first-page":"246","DOI":"10.1016\/S0894-7317(97)70062-2","article-title":"The noninvasive assessment of left ventricular diastolic function with two-dimensional and doppler echocardiography","volume":"10","author":"Oh","year":"1997","journal-title":"J Am Soc Echocardiogr."},{"key":"B22","doi-asserted-by":"publisher","first-page":"438","DOI":"10.1111\/jpi.12357","article-title":"The cardioprotective effect of melatonin and exendin-4 treatment in a rat model of cardiorenal syndrome","volume":"61","author":"Chua","year":"2016","journal-title":"J Pineal Res."},{"key":"B23","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1186\/s12882-015-0163-9","article-title":"Plasma levels of natriuretic peptides and development of chronic kidney disease","volume":"16","author":"Ogawa","year":"2015","journal-title":"BMC Nephrol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"2434","DOI":"10.1681\/ASN.2014060543","article-title":"Klotho protects against indoxyl sulphate-induced myocardial hypertrophy","volume":"26","author":"Yang","year":"2015","journal-title":"J Am Soc Nephrol"},{"key":"B25","doi-asserted-by":"publisher","first-page":"10530","DOI":"10.1002\/jcb.28339","article-title":"GDF-15 promotes mitochondrial function and proliferation in neuronal HT22 cells","volume":"120","author":"Liu","year":"2019","journal-title":"J Cell Biochem."},{"key":"B26","doi-asserted-by":"publisher","first-page":"11514","DOI":"10.1073\/pnas.94.21.11514","article-title":"MIC-1, a novel macrophage inhibitory cytokine, is a divergent member of the TGF-beta superfamily","volume":"94","author":"Bootcov","year":"1997","journal-title":"Proc Natl Acad Sci USA."},{"key":"B27","doi-asserted-by":"publisher","first-page":"462","DOI":"10.1016\/j.cjca.2018.12.027","article-title":"The role of gDF-15 in heart failure patients with chronic kidney disease","volume":"35","author":"Benes","year":"2019","journal-title":"Can J Cardiol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1093\/ndt\/gfr575","article-title":"Macrophage inhibitory cytokine-1 (MIC-1\/GDF15) and mortality in end-stage renal disease","volume":"27","author":"Breit","year":"2012","journal-title":"Nephrol Dial Transplant."},{"key":"B29","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1053\/j.ajkd.2018.03.025","article-title":"GDF-15, galectin 3, soluble ST2, and risk of mortality and cardiovascular events in CKD","volume":"72","author":"Tuegel","year":"2018","journal-title":"Am J Kidney Dis."},{"key":"B30","doi-asserted-by":"publisher","first-page":"444","DOI":"10.1038\/s41586-019-1911-y","article-title":"GDF15 mediates the effects of metformin on body weight and energy balance","volume":"578","author":"Coll","year":"2020","journal-title":"Nature."},{"key":"B31","doi-asserted-by":"publisher","first-page":"S31","DOI":"10.3109\/1354750X.2011.561498","article-title":"Novel biomarkers in human terminal heart failure and under mechanical circulatory support","volume":"16","author":"Kramer","year":"2011","journal-title":"Biomarkers."},{"key":"B32","doi-asserted-by":"publisher","first-page":"579","DOI":"10.1152\/ajprenal.00442.2014","article-title":"Mitochondrial dysfunction in uremic cardiomyopathy","volume":"308","author":"Taylor","year":"2015","journal-title":"Am J Physiol Renal Physiol."},{"key":"B33","doi-asserted-by":"publisher","first-page":"1370","DOI":"10.1038\/ki.2011.47","article-title":"Fibroblast growth factor 23 is elevated before parathyroid hormone and phosphate in chronic kidney disease","volume":"79","author":"Isakova","year":"2011","journal-title":"Kidney Int."},{"key":"B34","doi-asserted-by":"publisher","first-page":"344","DOI":"10.2215\/CJN.05840513","article-title":"Disordered FGF23 and mineral metabolism in children with CKD","volume":"9","author":"Portale","year":"2014","journal-title":"Clin J Am Soc Nephrol."},{"key":"B35","doi-asserted-by":"publisher","first-page":"F785","DOI":"10.1152\/ajprenal.00488.2015","article-title":"Oxalate-induced chronic kidney disease with its uremic and cardiovascular complications in C57BL\/6 mice","volume":"310","author":"Mulay","year":"2016","journal-title":"Am J Physiol Renal Physiol."},{"key":"B36","doi-asserted-by":"publisher","first-page":"e0191706","DOI":"10.1371\/journal.pone.0191706","article-title":"Fibroblast growth factor 23 is upregulated in the kidney in a chronic kidney disease rat model","volume":"13","author":"Sugiura","year":"2018","journal-title":"PLoS ONE."},{"key":"B37","doi-asserted-by":"publisher","first-page":"584","DOI":"10.1056\/NEJMoa0706130","article-title":"Fibroblast growth factor 23 and mortality among patients undergoing hemodialysis","volume":"359","author":"Guti\u00e9rrez","year":"2008","journal-title":"N Engl J Med."},{"key":"B38","doi-asserted-by":"publisher","first-page":"2545","DOI":"10.1161\/CIRCULATIONAHA.108.844506","article-title":"Fibroblast growth factor 23 and left ventricular hypertrophy in chronic kidney disease","volume":"119","author":"Guti\u00e9rrez","year":"2009","journal-title":"Circulation."},{"key":"B39","doi-asserted-by":"publisher","first-page":"1088","DOI":"10.1093\/ndt\/gfv421","article-title":"Induction of cardiac FGF23\/FGFR4 expression is associated with left ventricular hypertrophy in patients with chronic kidney disease","volume":"31","author":"Leifheit-Nestler","year":"2016","journal-title":"Nephrol Dial Transplant."},{"key":"B40","doi-asserted-by":"publisher","first-page":"767","DOI":"10.1093\/ndt\/gfv398","article-title":"Elevation of circulating but not myocardial FGF23 in human acute decompensated heart failure","volume":"31","author":"Andersen","year":"2016","journal-title":"Nephrol Dial Transplant"},{"key":"B41","doi-asserted-by":"publisher","first-page":"e016041","DOI":"10.1161\/JAHA.119.014566","article-title":"Clinical potential of targeting fibroblast growth factor-23 and \u03b1Klotho in the treatment of uremic cardiomyopathy","volume":"9","author":"Jonathan","year":"2020","journal-title":"J Am Heart Assoc."}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2021.690517\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,7,14]],"date-time":"2021-07-14T06:58:05Z","timestamp":1626245885000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2021.690517\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,14]]},"references-count":41,"alternative-id":["10.3389\/fmed.2021.690517"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2021.690517","relation":{},"ISSN":["2296-858X"],"issn-type":[{"value":"2296-858X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,14]]},"article-number":"690517"}}