title: Dehydroepiandrosterone fatty acyl esters in high density lipoprotein: interaction with human vascular endothelial cells and vascular responses ex vivo.
abstract: Dehydroepiandrosterone (DHEA) fatty acyl esters once incorporated in high density lipoprotein (HDL) induce a stronger vasodilatory response in rat mesenteric arteries ex vivo compared to native HDL. We studied the role of HDL receptor, scavenger receptor class B, type 1 (SR-B1), as well as estrogen and androgen receptors in the vasodilatory response of HDL-associated DHEA fatty acyl esters. Using cultured human vascular endothelial cells (HUVEC), we investigated the possible internalization and cellular response of HDL-associated DHEA esters. We prepared DHEA ester-enriched HDL by incubating human plasma in the presence of DHEA. After isolation and purification, HDL was added in cumulative doses to arterial rings precontracted with noradrenaline. Inhibition of the function of SR-B1 almost completely abolished maximal vasorelaxation by DHEA-enriched HDL while estrogen or androgen receptor blockage had no significant effect. When HUVECs were incubated in the presence of [³H]DHEA ester-enriched HDL, the amount of intracellular [³H]-radioactivity increased steadily during 24 h. Blocking of SR-B1 reduced this uptake by a mean of 30%. The proportion of unesterified [³H]DHEA, as analyzed by thin-layer chromatography, increased intracellularly and in the cell culture media after several hours of incubation of the cells in the presence of [³H]DHEA ester-enriched HDL. This indicated slow hydrolysis of DHEA fatty acyl esters and subsequent excretion of unesterified DHEA by the cells. In conclusion, DHEA-enriched HDL induced vasorelaxation via the SR-B1-facilitated pathway. However, this vasodilation is not likely to be attributed to rapid hydrolysis of HDL-associated DHEA esters by the vascular endothelium.
authors.affiliation: Department of Medicine, Helsinki University Central Hospital and Folkhälsan Research Center, 00290 Helsinki, Finland.
authors.forename: Hanna
authors.initials: H
authors.lastname: Paatela
authors.forename: Veera
authors.initials: V
authors.lastname: Vihma
authors.forename: Matti
authors.initials: M
authors.lastname: Jauhiainen
authors.forename: Eero
authors.initials: E
authors.lastname: Mervaala
authors.forename: Matti J
authors.initials: MJ
authors.lastname: Tikkanen
mesh_terms: D059002:Androgen Receptor Antagonists / Q000494:pharmacology; D000813:Anilides / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D003517:Cyclopentanes / Q000494:pharmacology; D003687:Dehydroepiandrosterone / Q000494:pharmacology* / Q000502:physiology; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D004952:Esters; D004965:Estrogen Antagonists / Q000494:pharmacology; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008075:Lipoproteins, HDL / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000494:pharmacology* / Q000502:physiology; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000378:metabolism*; D009570:Nitriles / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018110:Receptors, Lipoprotein / Q000037:antagonists & inhibitors / Q000187:drug effects; D013882:Thiosemicarbazones / Q000494:pharmacology; D014105:Tosyl Compounds / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: C526651:2-hexyl-1-cyclopentanone thiosemicarbazone; D059002:Androgen Receptor Antagonists; D000813:Anilides; D003517:Cyclopentanes; D004952:Esters; D004965:Estrogen Antagonists; D008075:Lipoproteins, HDL; D009570:Nitriles; D018110:Receptors, Lipoprotein; D013882:Thiosemicarbazones; D014105:Tosyl Compounds; D014665:Vasodilator Agents; C031616:high density lipoprotein receptors; D003687:Dehydroepiandrosterone; C053541:bicalutamide