biostudies-literatureYan LNCATS NIH HHSHoward Hughes Medical InstituteNHLBI NIH HHS1399-411https://www.ebi.ac.uk/biostudies/studies/S-EPMC4108264biostudies-literatureUnknown34(7)<h4>Objective</h4>S100A12 and fibroblast growth factor 23 are biomarkers of cardiovascular morbidity and mortality in patients with chronic kidney disease (CKD). We tested the hypothesis that human S100/calgranulin would accelerate cardiovascular disease in mice subjected to CKD.<h4>Approach and results</h4>A bacterial artificial chromosome of the human S100/calgranulin gene cluster containing the genes and regulatory elements for S100A8, S100A9, and S100A12 was expressed in C57BL/6J mouse (hBAC-S100) to generate a novel humanized mouse model. CKD was induced by ureteral ligation, and hBAC-S100 mice and wild-type mice were studied after 10 weeks of chronic uremia. hBAC-S100 mice with CKD showed increased fibroblast growth factor 23 in the hearts, left ventricular hypertrophy, diastolic dysArteriosclerosis, thrombosis, and vascular biologyS100/Calgranulin-mediated inflammation accelerates left ventricular hypertrophy and aortic valve sclerosis in chronic kidney disease in a receptor for advanced glycation end products-dependent manner.PMC41082641R01HL4821UL1 TR000430R01 HL114821Yan LEarley JPuri TSHofmann Bowman MAMathew LGardner BChellan BfalseS100/Calgranulin-mediated inflammation accelerates left ventricular hypertrophy and aortic valve sclerosis in chronic kidney disease in a receptor for advanced glycation end products-dependent manner.<h4>Objective</h4>S100A12 and fibroblast growth factor 23 are biomarkers of cardiovascular morbidity and mortality in patients with chronic kidney disease (CKD). We tested the hypothesis that human S100/calgranulin would accelerate cardiovascular disease in mice subjected to CKD.<h4>Approach and results</h4>A bacterial artificial chromosome of the human S100/calgranulin gene cluster containing the genes and regulatory elements for S100A8, S100A9, and S100A12 was expressed in C57BL/6J mouse (hBAC-S100) to generate a novel humanized mouse model. CKD was induced by ureteral ligation, and hBAC-S100 mice and wild-type mice were studied after 10 weeks of chronic uremia. hBAC-S100 mice with CKD showed increased fibroblast growth factor 23 in the hearts, left ventricular hypertrophy, diastolic dys2014-01-01T00:00:00Z2014 Jul2025-04-19T04:55:59.033Z2019-03-27T01:32:38ZS-EPMC41082642485505910.1161/ATVBAHA.114.30350810.1161/atvbaha.114.303508