title: Pitavastatin Reduces Inflammation in Atherosclerotic Plaques in Apolipoprotein E-Deficient Mice with Late Stage Renal Disease.
abstract: OBJECTIVE
  Chronic renal disease (CRD) accelerates atherosclerosis and cardiovascular calcification. Statins reduce low-density lipoprotein-cholesterol levels in patients with CRD, however, the benefits of statins on cardiovascular disease in CRD remain unclear. This study has determined the effects of pitavastatin, the newest statin, on arterial inflammation and calcification in atherogenic mice with CRD.
  
  
  RESULTS
  CRD was induced by 5/6 nephrectomy in cholesterol-fed apolipoprotein E-deficient mice. Mice were randomized into three groups: control mice, CRD mice, and CRD mice treated with pitavastatin. Ultrasonography showed that pitavastatin treatment significantly attenuated luminal stenosis in brachiocephalic arteries of CRD mice. Near-infrared molecular imaging and correlative Mac3 immunostaining demonstrated a significant reduction in macrophage accumulation in pitavastatin-treated CRD mice. Pitavastatin treatment reduced levels of osteopontin in plasma and atherosclerotic lesions in CRD mice, but did not produce a significant reduction in calcification in atherosclerotic plaques as assesses by histology. CRD mice had significantly higher levels of phosphate in plasma than did control mice, which did not change by pitavastatin. In vitro, pitavastatin suppressed the expression of osteopontin in peritoneal macrophages stimulated with phosphate or calcium/phosphate in concentrations similar to those found in human patients with CRD.
  
  
  CONCLUSIONS
  Our study provides in vivo evidence that pitavastatin reduces inflammation within atherosclerotic lesions in CRD mice.
authors.affiliation: Center for Interdisciplinary Cardiovascular Sciences (CICS), Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, 02115, United States of America.
authors.forename: Manabu
authors.initials: M
authors.lastname: Shibasaki
authors.affiliation: Center for Interdisciplinary Cardiovascular Sciences (CICS), Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, 02115, United States of America.
authors.forename: Jian-Guo
authors.initials: JG
authors.lastname: Wang
authors.affiliation: Center for Interdisciplinary Cardiovascular Sciences (CICS), Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, 02115, United States of America.
authors.forename: Jose-Luiz
authors.initials: JL
authors.lastname: Figueiredo
authors.affiliation: Center for Interdisciplinary Cardiovascular Sciences (CICS), Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, 02115, United States of America.
authors.forename: Sophie E P
authors.initials: SE
authors.lastname: New
authors.affiliation: Center for Excellence in Vascular Biology, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, 02114, United States of America.
authors.forename: Thibaut
authors.initials: T
authors.lastname: Quillard
authors.affiliation: Center for Interdisciplinary Cardiovascular Sciences (CICS), Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, 02115, United States of America.
authors.forename: Claudia
authors.initials: C
authors.lastname: Goettsch
authors.affiliation: Center for Excellence in Vascular Biology, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, 02114, United States of America.
authors.forename: Jun-ichiro
authors.initials: J
authors.lastname: Koga
authors.affiliation: Center for Interdisciplinary Cardiovascular Sciences (CICS), Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, 02115, United States of America.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Sonoki
authors.affiliation: Center for Interdisciplinary Cardiovascular Sciences (CICS), Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, 02115, United States of America.
authors.forename: Jiro
authors.initials: J
authors.lastname: Matsumoto
authors.affiliation: Center for Interdisciplinary Cardiovascular Sciences (CICS), Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, 02115, United States of America; Center for Excellence in Vascular Biology, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, 02114, United States of America.
authors.forename: Masanori
authors.initials: M
authors.lastname: Aikawa
authors.affiliation: Center for Interdisciplinary Cardiovascular Sciences (CICS), Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, 02115, United States of America; Center for Excellence in Vascular Biology, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, 02114, United States of America.
authors.forename: Elena
authors.initials: E
authors.lastname: Aikawa
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency*; D050197:Atherosclerosis / Q000097:blood / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000235:genetics; D002118:Calcium / Q000097:blood; D002784:Cholesterol / Q000009:adverse effects / Q000494:pharmacology; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood / Q000188:drug therapy* / Q000235:genetics; D017737:Macrophages, Peritoneal / Q000378:metabolism / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D053495:Osteopontin / Q000097:blood; D010710:Phosphates / Q000097:blood; D058226:Plaque, Atherosclerotic / Q000097:blood / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000235:genetics; D011804:Quinolines / Q000494:pharmacology*; D014463:Ultrasonography
chemical_list: D001057:Apolipoproteins E; D010710:Phosphates; D011804:Quinolines; D053495:Osteopontin; D002784:Cholesterol; C108475:pitavastatin; D002118:Calcium