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. The aging process may enhance lipoprotein modification, which leads to an increase in the susceptibility of low density lipoprotein (LDL) and high density 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 (dehydroepiandrosterone sulfate) and changes in their concentrations in HDL and LDL 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 demonstrated that vitamin E is unable to restore the decreased resistance to oxidation of LDL from elderly subjects to that of LDL obtained from young subjects. Furthermore, our results provide evidence that DHEA is an integral part of LDL and HDL and disappears to almost nondetectable levels during aging. 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 seems to act either by protecting vitamin E from disappearance from LDL under oxidation or by scavenging directly the free radicals produced during the oxidative process. Our results suggests that DHEA exerts an antioxidative effect on LDL, which could have antiatherogenic consequences. Careful clinical trials of DHEA replacement should determine whether this ex vivo effect could be translated into any measurable antiatherogenic (cardioprotective) action.
Khalil
A
A
Département de Médecine, Service de Gériatrie, Université de Sherbrooke, Sherbrooke, Quebec, Canada.
Fortin
J P
JP
LeHoux
J G
JG
Fülöp
T
T
D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D003687:Dehydroepiandrosterone / Q000097:blood / Q000494:pharmacology* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D005609:Free Radicals / Q000494:pharmacology / Q000528:radiation effects; D005720:Gamma Rays; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects* / Q000528:radiation effects; D008075:Lipoproteins, HDL / Q000097:blood / Q000187:drug effects / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000097:blood* / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D014810:Vitamin E / Q000097:blood / Q000494:pharmacology / Q000528:radiation effects
D005609:Free Radicals; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D014810:Vitamin E; D003687:Dehydroepiandrosterone