Lecithin/cholesterol acyltransferase induces estradiol esterification in high-density lipoprotein, increasing its antioxidant potential.
Endogenous estrogens protect against atherosclerosis, but the exact mechanisms remain unclear. One possibility is inhibition of lipoprotein oxidation. To act as antioxidants, estrogens reportedly need to be converted to lipophilic estrogen fatty acyl esters in a reaction catalyzed by lecithin/cholesterol acyltransferase (LCAT). To demonstrate directly that estradiol (E2) esters formed by LCAT and incorporated in high-density lipoprotein (HDL) increase its antioxidant potential, we investigated the copper-induced oxidation of purified HDL after incubations of: 1) HDL alone; 2) HDL in the presence of exogenous E2; 3) HDL in the presence of exogenous LCAT; 4) HDL in the presence of both E2 and LCAT; and 5) HDL in the presence of E2, LCAT, and the LCAT inhibitor DTNB. We used this in vitro model system with supraphysiological concentrations of E2 and purified LCAT to produce E2 ester-containing HDL particles for studies of oxidation resistance. The lag time of HDL oxidation significantly increased with increasing contents of HDL-associated E2 esters. In conclusion, our results clearly demonstrated the role of LCAT in E2 esterification and its involvement in antioxidant protection of HDL. Elucidation of the possible in vivo role of HDL-associated estrogen esters requires further critical studies including experiments with physiological hormone concentrations.
Höckerstedt
Anna
A
Department of Medicine, Helsinki University Central Hospital, Finland. anna.hockerstedt@hus.fi <anna.hockerstedt@hus.fi>
Jauhiainen
Matti
M
Tikkanen
Matti J
MJ
D000975:Antioxidants / Q000378:metabolism*; D003300:Copper / Q000378:metabolism; D004951:Esterification; D004958:Estradiol / Q000378:metabolism*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008075:Lipoproteins, HDL / Q000378:metabolism*; D008297:Male; D010084:Oxidation-Reduction; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000378:metabolism*
D000975:Antioxidants; D008075:Lipoproteins, HDL; D004958:Estradiol; D003300:Copper; D007862:Phosphatidylcholine-Sterol O-Acyltransferase