TY - JOUR
T1 - ATP binding cassette G1-dependent cholesterol efflux during inflammation
AU - De Beer, Maria C.
AU - Ji, Ailing
AU - Jahangiri, Anisa
AU - Vaughan, Ashley M.
AU - De Beer, Frederick C.
AU - Van Der Westhuyzen, Deneys R.
AU - Webb, Nancy R.
PY - 2011/2
Y1 - 2011/2
N2 - ATP binding cassette transporter G1 (ABCG1) mediates the transport of cellular cholesterol to HDL, and it plays a key role in maintaining macrophage cholesterol homeostasis. During inflammation, HDL undergoes substantial remodeling, acquiring lipid changes and serum amyloid A (SAA) as a major apolipoprotein. In the current study, we investigated whether remodeling of HDL that occurs during acute inflammation impacts ABCG1-dependent effl ux. Our data indicate that lipid free SAA acts similarly to apolipoprotein A-I (apoA-I) in mediating sequential efflux from ABCA1 and ABCG1. Compared with normal mouse HDL, acute phase (AP) mouse HDL containing SAA exhibited a modest but significant 17% increase in ABCG1-dependent efflux. Interestingly, AP HDL isolated from mice lacking SAA (SAAKO mice) was even more effective in promoting ABCG1 efflux. Hydrolysis with Group IIA secretory phospholipase A2 (sPLA2-IIA) significantly reduced the ability of AP HDL from SAAKO mice to serve as a substrate for ABCG1-mediated cholesterol transfer, indicating that phospholipid (PL) enrichment, and not the presence of SAA, is responsible for alterations in efflux. AP human HDL, which is not PL-enriched, was somewhat less effective in mediating ABCG1-dependent efflux compared with normal human HDL. Our data indicate that inflammatory remodeling of HDL impacts ABCG1-dependent efflux independent of SAA.
AB - ATP binding cassette transporter G1 (ABCG1) mediates the transport of cellular cholesterol to HDL, and it plays a key role in maintaining macrophage cholesterol homeostasis. During inflammation, HDL undergoes substantial remodeling, acquiring lipid changes and serum amyloid A (SAA) as a major apolipoprotein. In the current study, we investigated whether remodeling of HDL that occurs during acute inflammation impacts ABCG1-dependent effl ux. Our data indicate that lipid free SAA acts similarly to apolipoprotein A-I (apoA-I) in mediating sequential efflux from ABCA1 and ABCG1. Compared with normal mouse HDL, acute phase (AP) mouse HDL containing SAA exhibited a modest but significant 17% increase in ABCG1-dependent efflux. Interestingly, AP HDL isolated from mice lacking SAA (SAAKO mice) was even more effective in promoting ABCG1 efflux. Hydrolysis with Group IIA secretory phospholipase A2 (sPLA2-IIA) significantly reduced the ability of AP HDL from SAAKO mice to serve as a substrate for ABCG1-mediated cholesterol transfer, indicating that phospholipid (PL) enrichment, and not the presence of SAA, is responsible for alterations in efflux. AP human HDL, which is not PL-enriched, was somewhat less effective in mediating ABCG1-dependent efflux compared with normal human HDL. Our data indicate that inflammatory remodeling of HDL impacts ABCG1-dependent efflux independent of SAA.
KW - ATP binding cassette AI
KW - High density lipoprotein
KW - Macrophage
KW - Reverse cholesterol transport
KW - Serum amyloid A
UR - http://www.scopus.com/inward/record.url?scp=78751525894&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=78751525894&partnerID=8YFLogxK
U2 - 10.1194/jlr.M012328
DO - 10.1194/jlr.M012328
M3 - Article
C2 - 21138980
AN - SCOPUS:78751525894
SN - 0022-2275
VL - 52
SP - 345
EP - 353
JO - Journal of Lipid Research
JF - Journal of Lipid Research
IS - 2
ER -