Effect of dehydroepiandrosterone on atherosclerosis in apolipoprotein E-deficient mice.
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.
Yamakawa
Tadashi
T
Department of Endocrinology and Diabetes, Yokohama City University Medical Center, Yokohama, Japan. yamakat@urahp.yokohama-cu.ac.jp
Ogihara
Kikumi
K
Nakamura
Misa
M
Utsunomiya
Hirotoshi
H
Kadonosono
Kazuaki
K
Kishikawa
Seigo
S
Terauchi
Yasuo
Y
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
D001057:Apolipoproteins E; D018932:Chemokine CCL2; D014280:Triglycerides; D003687:Dehydroepiandrosterone; D002784:Cholesterol