Age-related decrease of dehydroepiandrosterone concentrations in low density lipoproteins and its role in the susceptibility of low density lipoproteins to lipid peroxidation

The incidence of atherosclerosis and related diseases increases with age. T he aging process may enhance lipoprotein modification, which leads to an in crease in the susceptibility of low density lipoprotein (LDL) and high dens ity lipoprotein (HDL) to oxidation, Dehydroepiandrosterone (DHEA), the most abundant steroid hormone in humans, has been shown to have antiatherogenic effects. This hormone also decreases dramatically with age. In the present study, we were interested in determining the presence of DHEA/DHEAS (dehyd roepiandrosterone sulfate) and changes in their concentrations in HDL and L DL lipoproteins with age. Moreover, we studied the susceptibility of LDL to oxidation with age in the presence or absence of vitamin E or DHEA, We dem onstrated that vitamin E is unable to restore the decreased resistance to o xidation of LDL from elderly subjects to that of LDL obtained from young su bjects. Furthermore, our results provide evidence that DHEA is an integral part of LDL and HDL and disappears to almost nondetectable levels during ag ing. The DHEA incorporated into the LDL from elderly subjects increased LDL resistance to oxidation in a concentration-dependent manner. The increased resistance provided by DHEA was higher than that with vitamin E. DHEA seem s to act either by protecting vitamin E from disappearance from LDL under o xidation or by scavenging directly the free radicals produced during the ox idative process. Our results suggest that DHEA exerts an antioxidative effe ct on LDL, which could have antiatherogenic consequences. Careful clinical trials of DHEA replacement should determine whether this ex vivo effect cou ld be translated into any measurable antiatherogenic (cardioprotective) act ion.