title: SR-BI in bone marrow derived cells protects mice from diet induced coronary artery atherosclerosis and myocardial infarction.
abstract: SR-BI deficient mice that are also hypomorphic for apolipoprotein E expression develop diet induced occlusive coronary artery atherosclerosis, myocardial infarction and early death. To test the role of SR-BI in bone marrow derived cells, we used bone marrow transplantation to generate SR-BI-null; apoE-hypomorphic mice in which SR-BI expression was restored solely in bone marrow derived cells. SR-BI-null; apoE-hypomorphic mice were transplanted with SR-BI(+/+)apoE-hypomorphic, or control, autologous SR-BI-null; apoE-hypomorphic bone marrow. Four weeks later, mice were fed a high-fat, high-cholesterol, cholate-containing diet to induce coronary artery atherosclerosis. Mice transplanted with autologous bone marrow developed extensive aortic atherosclerosis and severe occlusive coronary artery atherosclerosis after 4 weeks of feeding. This was accompanied by myocardial fibrosis and increased heart weights. In contrast, restoration of SR-BI expression in bone marrow derived-cells reduced diet induced aortic and coronary artery atherosclerosis, myocardial fibrosis and the increase in heart weights in SR-BI-null; apoE-hypomorphic mice. Restoration of SR-BI in bone marrow derived cells did not, however, affect steady state lipoprotein cholesterol levels, but did reduce plasma levels of IL-6. Monocytes from SR-BI-null mice exhibited a greater capacity to bind to VCAM-1 and ICAM-1 than those from SR-BI(+/+) mice. Furthermore, restoration of SR-BI expression in bone marrow derived cells attenuated monocyte recruitment into atherosclerotic plaques in mice fed high fat, high cholesterol cholate containing diet. These data demonstrate directly that SR-BI in bone marrow-derived cells protects against both aortic and CA atherosclerosis.
authors: Department of Biochemistry and Biomedical Sciences and Thrombosis and Atherosclerosis Research Institute, McMaster University, Hamilton, Ontario, Canada.
authors: Ying
authors: Y
authors: Pei
authors: Xing
authors: X
authors: Chen
authors: Dina
authors: D
authors: Aboutouk
authors: Mark T
authors: MT
authors: Fuller
authors: Omid
authors: O
authors: Dadoo
authors: Pei
authors: P
authors: Yu
authors: Elizabeth J
authors: EJ
authors: White
authors: Suleiman A
authors: SA
authors: Igdoura
authors: Bernardo L
authors: BL
authors: Trigatti
mesh_terms: D000818:Animals; D001011:Aorta / Q000473:pathology; D001057:Apolipoproteins E / Q000172:deficiency; D001854:Bone Marrow Cells / Q000378:metabolism*; D016026:Bone Marrow Transplantation; D018955:CD36 Antigens / Q000235:genetics* / Q000378:metabolism; D003324:Coronary Artery Disease / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D003331:Coronary Vessels / Q000378:metabolism / Q000473:pathology; D004032:Diet; D004195:Disease Models, Animal; D005260:Female; D005355:Fibrosis; D018836:Inflammation Mediators / Q000097:blood / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008055:Lipids / Q000097:blood; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D009203:Myocardial Infarction / Q000235:genetics* / Q000628:therapy; D009206:Myocardium / Q000473:pathology; D009929:Organ Size; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: D001057:Apolipoproteins E; D018955:CD36 Antigens; D018836:Inflammation Mediators; D008055:Lipids; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1
references: J Biol Chem. 1999 Jan 22;274(4):2366-71
references: 9891004
references: Proc Natl Acad Sci U S A. 1997 Nov 11;94(23):12610-5
references: 9356497
references: Arterioscler Thromb Vasc Biol. 1997 Nov;17(11):3117-26
references: 9409301
references: Proc Natl Acad Sci U S A. 2001 Sep 25;98(20):11587-91
references: 11553788
references: Proc Natl Acad Sci U S A. 2003 Jun 10;100(12):7283-8
references: 12771386
references: Nat Med. 2001 Jul;7(7):853-7
references: 11433352
references: J Clin Invest. 2007 Jan;117(1):185-94
references: 17200718
references: J Mol Med (Berl). 2006 Apr;84(4):276-94
references: 16501936
references: Arterioscler Thromb Vasc Biol. 2003 May 1;23(5):712-9
references: 12615688
references: J Leukoc Biol. 2011 Aug;90(2):313-21
references: 21551251
references: Arterioscler Thromb Vasc Biol. 2006 Mar;26(3):548-54
references: 16397139
references: J Lipid Res. 2004 Nov;45(11):2088-95
references: 15314100
references: J Clin Invest. 1995 Aug;96(2):1118-24
references: 7635947
references: Circulation. 2005 Jun 28;111(25):3457-64
references: 15967843
references: Arterioscler Thromb Vasc Biol. 2000 Mar;20(3):721-7
references: 10712397
references: J Biol Chem. 2003 Jun 27;278(26):23699-705
references: 12639961
references: Arterioscler Thromb Vasc Biol. 2008 Nov;28(11):2071-7
references: 18617650
references: J Clin Invest. 1996 Aug 15;98(4):984-95
references: 8770871
references: Arterioscler Thromb Vasc Biol. 2003 Sep 1;23(9):1589-94
references: 12829524
references: Arterioscler Thromb Vasc Biol. 2007 Nov;27(11):2292-301
references: 17673705
references: Circulation. 2003 Nov 4;108(18):2258-63
references: 14581413
references: Arterioscler Thromb Vasc Biol. 2003 May 1;23(5):898-904
references: 12649086
references: J Lipid Res. 2001 Feb;42(2):170-80
references: 11181745
references: Arterioscler Thromb Vasc Biol. 2006 Feb;26(2):242-9
references: 16373607
references: J Lipid Res. 2007 Feb;48(2):405-16
references: 17079793
references: Arterioscler Thromb Vasc Biol. 2005 Apr;25(4):803-8
references: 15692099
references: J Biol Chem. 1999 Mar 12;274(11):7165-71
references: 10066776
references: Immunobiology. 2006;211(6-8):609-18
references: 16920499
references: J Biol Chem. 2002 Mar 29;277(13):11064-8
references: 11792702
references: Proc Natl Acad Sci U S A. 1999 Aug 3;96(16):9322-7
references: 10430941
references: J Immunol. 2004 Apr 1;172(7):4410-7
references: 15034056
references: Trends Immunol. 2003 Jan;24(1):25-9
references: 12495721
references: Horm Metab Res. 2001 Jul;33(7):389-93
references: 11507674
references: J Lipid Res. 1998 Mar;39(3):495-508
references: 9548583
references: Am J Physiol Cell Physiol. 2010 Jun;298(6):C1538-48
references: 20219948
references: Circ Res. 2002 Feb 22;90(3):270-6
references: 11861414
references: J Virol. 2008 Apr;82(7):3466-79
references: 18216094
references: Blood. 2000 Jan 15;95(2):602-9
references: 10627469
references: Arterioscler Thromb Vasc Biol. 2011 Nov;31(11):2543-51
references: 21836069
references: J Biol Chem. 1998 Dec 4;273(49):32920-6
references: 9830042
references: Nat Rev Cardiol. 2010 Feb;7(2):77-86
references: 20065951
references: Biochim Biophys Acta. 2010 Dec;1801(12):1239-48
references: 20732452
references: Br J Haematol. 2000 Jul;110(1):71-81
references: 10930981
references: J Clin Invest. 2005 Oct;115(10):2870-4
references: 16200214
references: Nature. 1997 May 22;387(6631):414-7
references: 9163428
references: Circ Res. 1999 Jul 9;85(1):108-16
references: 10400916
references: J Biol Chem. 2000 Jul 7;275(27):20368-73
references: 10751392
references: Arterioscler Thromb Vasc Biol. 2000 Apr;20(4):1068-73
references: 10764675
references: Arterioscler Thromb Vasc Biol. 2006 Jan;26(1):150-6
references: 16269665
references: Am J Pathol. 2004 Sep;165(3):785-94
references: 15331403
references: Am J Pathol. 2011 Oct;179(4):1693-705
references: 21835155
references: Proc Natl Acad Sci U S A. 1998 Apr 14;95(8):4619-24
references: 9539787
references: Arterioscler Thromb Vasc Biol. 1999 Oct;19(10):2364-7
references: 10521365
references: Arterioscler Thromb Vasc Biol. 2005 Jan;25(1):143-8
references: 15528479
references: J Med Virol. 2012 Nov;84(11):1727-36
references: 22997075