{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T15:45:29Z","timestamp":1790610329586,"version":"4.1.0"},"reference-count":41,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2014,5,22]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              Cardiovascular diseases such as atherosclerosis and vascular calcification are a major cause of death in patients with chronic kidney disease (\n              <jats:styled-content style=\"fixed-case\">CKD<\/jats:styled-content>\n              ). Recently, the long\u2010awaited results of the Study of Heart and Renal Protection trial were reported. This large randomized clinical trial found that an extensive cholesterol\u2010lowering therapy through the combination of simvastatin and ezetimibe significantly reduced cardiovascular diseases in a wide range of patients with\n              <jats:styled-content style=\"fixed-case\">CKD<\/jats:styled-content>\n              . However, the mechanism by which this cholesterol\u2010lowering therapy reduces\n              <jats:styled-content style=\"fixed-case\">CKD<\/jats:styled-content>\n              \u2010dependent vascular diseases remains elusive. The objective of the present study was to determine the contribution of the oxysterol\u2010induced pro\u2010apoptotic transcription factor CCAAT\/enhancer\u2010binding protein homologous protein (\n              <jats:styled-content style=\"fixed-case\">CHOP<\/jats:styled-content>\n              ) on the pathogenesis of\n              <jats:styled-content style=\"fixed-case\">CKD<\/jats:styled-content>\n              \u2010dependent cardiovascular diseases through endoplasmic reticulum stress signaling.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              <jats:styled-content style=\"fixed-case\">CKD<\/jats:styled-content>\n              increased levels of serum oxysterols such as 7\u2010ketocholesterol in human patients and ApoE\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              mice. Treatment with simvastatin plus ezetimibe strongly reduced levels of serum oxysterols and attenuated\n              <jats:styled-content style=\"fixed-case\">CKD<\/jats:styled-content>\n              \u2010dependent atherosclerosis, vascular cell death, vascular calcification, and cardiac dysfunction. This therapy also reduced aortic endoplasmic reticulum stress induced by\n              <jats:styled-content style=\"fixed-case\">CKD<\/jats:styled-content>\n              . The short hairpin\n              <jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>\n              \u2010mediated knockdown of\n              <jats:styled-content style=\"fixed-case\">CHOP<\/jats:styled-content>\n              and activating transcription factor\u20104 in vascular smooth muscle cells attenuated oxysterol\u2010induced mineralization, osteogenic differentiation, and endoplasmic reticulum stress. In addition,\n              <jats:styled-content style=\"fixed-case\">CHOP<\/jats:styled-content>\n              deficiency protected ApoE\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              mice from\n              <jats:styled-content style=\"fixed-case\">CKD<\/jats:styled-content>\n              \u2010dependent vascular calcification, cardiac dysfunction, and vascular cell death.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              These data reveal that the cholesterol\u2010lowering therapy of simvastatin plus ezetimibe attenuates\n              <jats:styled-content style=\"fixed-case\">CKD<\/jats:styled-content>\n              \u2010dependent vascular diseases through a reduction of oxysterol\u2010mediated endoplasmic reticulum stress.\n              <jats:styled-content style=\"fixed-case\">CHOP<\/jats:styled-content>\n              plays a crucial role in the pathogenesis of\n              <jats:styled-content style=\"fixed-case\">CKD<\/jats:styled-content>\n              \u2010dependent vascular calcification.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.114.000949","type":"journal-article","created":{"date-parts":[[2014,6,25]],"date-time":"2014-06-25T03:45:30Z","timestamp":1403667930000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":55,"title":["Endoplasmic Reticulum Stress Effector CCAAT\/Enhancer\u2010binding Protein Homologous Protein (CHOP) Regulates Chronic Kidney Disease\u2013Induced Vascular Calcification"],"prefix":"10.1161","volume":"3","author":[{"given":"Shinobu","family":"Miyazaki\u2010Anzai","sequence":"first","affiliation":[{"name":"Division of Renal Diseases and Hypertension, University of Colorado Denver, Aurora, 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CO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rumiko","family":"Masuda","sequence":"additional","affiliation":[{"name":"Division of Renal Diseases and Hypertension, University of Colorado Denver, Aurora, CO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristen","family":"Jablonski","sequence":"additional","affiliation":[{"name":"Division of Renal Diseases and Hypertension, University of Colorado Denver, Aurora, CO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria A.","family":"Cavasin","sequence":"additional","affiliation":[{"name":"Division of Cardiology, University of Colorado Denver, Aurora, CO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Kendrick","sequence":"additional","affiliation":[{"name":"Division of Renal Diseases and Hypertension, University of Colorado Denver, Aurora, 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