title: Effect of dehydroepiandrosterone on atherosclerosis in apolipoprotein E-deficient mice.
abstract: OBJECTIVE
  Several clinical trials have indicated that dehydroepiandrosterone (DHEA) reduces coronary events associated with atherosclerosis. The aim of this study was to examine the inhibitory effect of DHEA on atherosclerosis and the mechanisms involved.
  
  
  METHODS
  Apolipoprotein E-knockout (apoE-KO) mice were fed an atherogenic high-cholesterol diet with or without 0.4% (w/w) DHEA for 12 weeks.
  
  
  RESULTS
  Although the plasma cholesterol and triglyceride levels were not decreased by DHEA, atherosclerotic lesions in the aortic sinus showed a 45% reduction in area with DHEA treatment versus untreated mice (0.19 +/- 0.01 vs. 0.10 +/- 0.02 microm(2); p<0.05). Accumulation of macrophages in aortic lesions was also markedly reduced in the DHEA group, and the macrophage-positive area decreased to 0.33 +/- 0.06 microm(2) from 0.67 +/- 0.07 microm(2) (p<0.01). Furthermore, DHEA suppressed the expression of monocyte chemoattractant protein-1 in the vessel wall. Thus, inhibition of macrophage infiltration by DHEA reduced the formation of atherosclerotic lesions in apoE-KO mice.
  
  
  CONCLUSIONS
  DHEA might be an effective agent for clinical management of atherosclerosis, but a larger controlled trial is necessary for confirmation.
authors.affiliation: Department of Endocrinology and Diabetes, Yokohama City University Medical Center, Yokohama, Japan. yamakat@urahp.yokohama-cu.ac.jp
authors.forename: Tadashi
authors.initials: T
authors.lastname: Yamakawa
authors.forename: Kikumi
authors.initials: K
authors.lastname: Ogihara
authors.forename: Misa
authors.initials: M
authors.lastname: Nakamura
authors.forename: Hirotoshi
authors.initials: H
authors.lastname: Utsunomiya
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Kadonosono
authors.forename: Seigo
authors.initials: S
authors.lastname: Kishikawa
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Terauchi
mesh_terms: D000818:Animals; D001018:Aortic Diseases / Q000188:drug therapy; D001057:Apolipoproteins E / Q000172:deficiency*; D050197:Atherosclerosis / Q000188:drug therapy*; D018932:Chemokine CCL2 / Q000096:biosynthesis; D002784:Cholesterol / Q000097:blood; D003687:Dehydroepiandrosterone / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D004353:Drug Evaluation, Preclinical; D008264:Macrophages; D051379:Mice; D018345:Mice, Knockout; D014280:Triglycerides / Q000097:blood
chemical_list: D001057:Apolipoproteins E; D018932:Chemokine CCL2; D014280:Triglycerides; D003687:Dehydroepiandrosterone; D002784:Cholesterol