oxHDL decreases the expression of CD36 on human macrophages through PPARgamma and p38 MAP kinase dependent mechanisms.
CD36, belongs to class B scavenger receptor family, is a macrophage receptor for oxidized low-density lipoprotein (oxLDL) and has been proven to play a critical role in atherosclerotic foam cell formation. In addition, CD36 expression is regulated by many factors including oxLDL and HDL. A recent study suggests that CD36 can also bind with oxidized high-density lipoprotein (oxHDL). However, the direct role of oxHDL in atherosclerosis is still not clear and it is not known whether oxHDL has any influence on the expression of CD36 in macrophages. Here, we performed experiments to investigate the effect of oxHDL on the expression of CD36 on human peripheral blood monocytes-macrophages and the possible mechanisms. Our results suggest that the uptake of oxHDL by CD36 on macrophages accelerates foam cell formation. In addition, oxHDL can down-regulate both the mRNA and surface protein expression of CD36 on human peripheral macrophages in vitro. oxHDL increased the mRNA expression and protein phosphorylation of peroxisome proliferators-activated receptor-gamma (PPARgamma). Using different mitogen-activated protein kinase (MAPK) inhibitors, we demonstrated that oxHDL regulated CD36 and PPARgamma expression in a p38-MAP kinase dependent mechanism.
Ren
Jingyi
J
Department of cardiology, Peking University People's Hospital, Beijing, China.
Jin
Wenying
W
Chen
Hong
H
D015153:Blotting, Western; D018955:CD36 Antigens / Q000378:metabolism*; D002478:Cells, Cultured; D005434:Flow Cytometry; D005487:Foam Cells / Q000378:metabolism; D006801:Humans; D008075:Lipoproteins, HDL / Q000737:chemistry* / Q000378:metabolism*; D008264:Macrophages / Q000166:cytology / Q000378:metabolism*; D009000:Monocytes / Q000166:cytology / Q000378:metabolism; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D018955:CD36 Antigens; D008075:Lipoproteins, HDL; D047495:PPAR gamma; D012333:RNA, Messenger; D048051:p38 Mitogen-Activated Protein Kinases
Free Radic Biol Med. 2006 May 15;40(10):1796-803
16678017
Nat Med. 2001 Jan;7(1):41-7
11135614
J Biol Chem. 1999 Jan 1;274(1):41-7
9867808
J Clin Invest. 1995 Oct;96(4):1859-65
7560077
Curr Opin Genet Dev. 1995 Oct;5(5):571-6
8664544
J Biol Chem. 2002 Jun 28;277(26):23582-6
11953427
J Clin Invest. 2005 Aug;115(8):2192-201
16075060
J Biol Chem. 2002 Dec 20;277(51):49982-8
12376530
Curr Opin Cardiol. 2008 Jul;23(4):370-8
18520722
J Clin Invest. 2000 Apr;105(8):1049-56
10772649
J Biol Chem. 1999 Jul 2;274(27):19055-62
10383407
Atherosclerosis. 2006 Jan;184(1):1-7
16157342
Biochim Biophys Acta. 2000 Jan 17;1483(2):217-35
10634938
J Biol Chem. 1951 Nov;193(1):265-75
14907713
FASEB J. 2001 Apr;15(6):1095-7
11292679
Proc Natl Acad Sci U S A. 2004 Aug 31;101(35):13032-7
15326314
Circulation. 2004 Feb 17;109(6):790-6
14970117
J Lipid Res. 2000 May;41(5):688-96
10787429
Ann Clin Biochem. 2000 Mar;37 ( Pt 2):179-86
10735361
FEBS Lett. 2007 Mar 20;581(6):1227-32
17346709
Arterioscler Thromb Vasc Biol. 2003 Sep 1;23(9):1583-8
12855483
Br J Haematol. 2004 Oct;127(1):97-104
15384983
Int J Biochem Cell Biol. 2007;39(11):2012-30
17466567
J Mol Biol. 2008 Feb 29;376(4):997-1007
18190928
Biochem Pharmacol. 2004 Jan 15;67(2):303-13
14698043
Circ Res. 2004 Oct 29;95(9):858-66
15514167
Cardiovasc Res. 2007 Aug 1;75(3):468-77
17442283
Cardiovasc Res. 2007 Aug 1;75(3):566-74
17524375
Vascul Pharmacol. 2004 May-Jun;41(4-5):139-46
15607497