Effect of Dehydroepiandrosterone on Atherosclerosis in Apolipoprotein E-Deficient Mice

Aim: 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 mu m(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 mu m(2) from 0.67 +/- 0.07 mu m(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.