HDL-associated dehydroepiandrosterone fatty acyl esters: enhancement of vasodilatory effect of HDL.
OBJECTIVE
Dehydroepiandrosterone (DHEA) and high-density lipoprotein (HDL) are both vascular relaxants. In the circulation, HDL transports DHEA fatty acyl esters (DHEA-FAEs), which are naturally occurring lipophilic derivatives of DHEA. We studied in isolated rat mesenteric arteries whether HDL-associated DHEA-FAE improves the vasodilatory effect of HDL.


RESULTS
To prepare DHEA-FAE-enriched HDL, we incubated DHEA with human plasma. After incubation, HDL was isolated, purified, and added in cumulative doses (0.1-125 microg/ml) to noradrenaline-precontracted rat arterial rings. DHEA-FAE-enriched HDL caused a dose-dependent relaxation (maximal 43+/-4%), which was significantly stronger than the effect of HDL from the control incubation without addition of DHEA (25+/-2%, p<0.001). When plasma incubation of DHEA was carried out in the presence of lecithin:cholesterol acyltransferase (LCAT) inhibitor, the relaxation response to HDL (25+/-3%) did not differ from the control HDL (p=0.98). Pretreatment of the arterial rings with nitric oxide synthase (NOS) antagonist impaired the relaxation response to DHEA-FAE-enriched HDL (43+/-4% vs. 30+/-3%, p=0.008). Similar experiments were performed with 17beta-estradiol (E(2)). Compared to control HDL, E(2)-FAE-enriched HDL induced slightly but non-significantly stronger relaxation.


CONCLUSIONS
DHEA-FAE-enriched HDL was a stronger vasodilator than native HDL, and vascular relaxation was in part mediated by NOS, suggesting that DHEA-FAE may improve HDL's antiatherogenic function.
Paatela
Hanna
H
Department of Medicine, Helsinki University Central Hospital and Folkhälsan Research Center, 00290 Helsinki, Finland. hanna.paatela@helsinki.fi
Mervaala
Eero
E
Deb
Somdatta
S
Wähälä
Kristiina
K
Tikkanen
Matti J
MJ
D000818:Animals; D003687:Dehydroepiandrosterone / Q000097:blood / Q000737:chemistry* / Q000378:metabolism*; D004952:Esters / Q000737:chemistry*; D006801:Humans; D066298:In Vitro Techniques; D008075:Lipoproteins, HDL / Q000378:metabolism* / Q000494:pharmacology*; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D014664:Vasodilation / Q000187:drug effects*
D004952:Esters; D008075:Lipoproteins, HDL; D003687:Dehydroepiandrosterone