Dehydroepiandosterone feeding prevents aortic fatty streak formation and cholesterol accumulation in cholesterol-fed rabbit

Abstract

The concentration of dehydroepiandrosterone sulfate (DHEA-S) in human plasma is higher than any other steroid. Recent evidence has suggested an inverse relationship between plasma DHEA levels and the development of coronary atherosclerosis in humans. We used the cholesterol-fed rabbit model to investigate whether DHEA feeding would diminish aortic fatty streak formation in this model. Fifteen New Zealand White rabbits were fed rabbit chow supplemented with 0.5% cholesterol (wt/wt). Seven animals were, in addition, fed DHEA, 0.5% of diet (wt/wt). Animals were sacrificed after 2 months, and the aortic involvement with fatty streaks was evaluated by computerized planimetry of Sudan IV-stained aortas and by chemical analysis of aortic wall lipids. Compared to controls, DHEA-fed animals had similar plasma levels of total, very low density lipoprotein (VLDL), low density lipoprotein (LDL), and high density lipoprotein (HDL) cholesterol, corticoids, and estrogens. DHEA-fed animals had higher plasma levels of total, VLDL, and LDL triglycerides and lower HDL triglycerides than did controls. DHEA feeding resulted in 30% and 40%, respectively, inhibition of fatty streak formation by chemical analysis and planimetry. We conclude that DHEA feeding inhibits the development of aortic fatty streaks in cholesterol-fed rabbits, independent of changes in plasma total and LDL cholesterol levels or DHEA conversion to estrogens or corticoids.