Cellular SR-BI and ABCA1-mediated cholesterol efflux are gender-specific in healthy subjects.
We evaluated the impact of gender differences in both the quantitative and qualitative features of HDL subspecies on cellular free cholesterol efflux through the scavenger receptor class B type I (SR-BI), ABCA1, and ABCG1 pathways. For that purpose, healthy subjects (30 men and 26 women) matched for age, body mass index, triglyceride, apolipoprotein A-I, and high density lipoprotein-cholesterol (HDL-C) levels were recruited. We observed a significant increase (+14%; P < 0.03) in the capacity of whole sera from women to mediate cellular free cholesterol efflux via the SR-BI-dependent pathway compared with sera from men. Such enhanced efflux capacity resulted from a significant increase in plasma levels of large cholesteryl ester-rich HDL2 particles (+20%; P < 0.04) as well as from an enhanced capacity (+14%; P < 0.03) of these particles to mediate cellular free cholesterol efflux via SR-BI. By contrast, plasma from men displayed an enhanced free cholesterol efflux capacity (+31%; P < 0.001) via the ABCA1 transporter pathway compared with that from women, which resulted from a 2.4-fold increase in the plasma level of prebeta particles (P < 0.008). Moreover, in women, SR-BI-mediated cellular free cholesterol efflux was significantly correlated with plasma HDL-C (r = 0.72, P < 0.0001), whereas this relationship was not observed in men. In conclusion, HDL-C level may not represent the absolute indicator of the efficiency of the initial step of the reverse cholesterol transport.
Institut National de la Santé et de la Recherche Médicale, UMR_S551, Dyslipoproteinemia and Atherosclerosis, Paris, France.
Giovanna
G
Catalano
Emilie
E
Duchene
Zélie
Z
Julia
Wilfried
W
Le Goff
Eric
E
Bruckert
M John
MJ
Chapman
Maryse
M
Guerin
D064286:ATP Binding Cassette Transporter 1; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D002784:Cholesterol / Q000378:metabolism*; D005260:Female; D006801:Humans; D008075:Lipoproteins, HDL / Q000378:metabolism; D053439:Lipoproteins, HDL2 / Q000378:metabolism; D008297:Male; D051122:Scavenger Receptors, Class B / Q000378:metabolism*; D012737:Sex Factors
C577836:ABCA1 protein, human; C419353:ABCG1 protein, human; D064286:ATP Binding Cassette Transporter 1; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters; D008075:Lipoproteins, HDL; D053439:Lipoproteins, HDL2; C495124:SCARB1 protein, human; D051122:Scavenger Receptors, Class B; D002784:Cholesterol