Smooth muscle cell biglycan overexpression results in increased lipoprotein retention on extracellular matrix: implications for the retention of lipoproteins in atherosclerosis.
Lipoprotein retention on extracellular matrix (ECM) may play a central role in atherogenesis, and a specific extracellular matrix proteoglycan, biglycan, has been implicated in lipoprotein retention in human atherosclerosis. To test whether increased cellular biglycan expression results in increased retention of lipoproteins on ECM, rat aortic smooth muscle cells (SMCs) were transduced with a human biglycan cDNA-containing retroviral vector (LBSN) or with an empty retroviral vector (LXSN). To assess the importance of biglycan's glycosaminoglycan side chains in lipoprotein retention, ECM binding studies were also performed using RASMCs transduced with a retroviral vector encoding for a mutant, glycosaminoglycan-deficient biglycan (LBmutSN). Human biglycan mRNA and protein were confirmed in LBSN and LBmutSN RASMCs by Northern and Western blot analyses. HDL3+E binding to SMC ECM was increased significantly (as determined by 95% confidence intervals for binding curves) for LBSN as compared to either LXSN or LBmutSN cells; the increases for LBSN cell ECM were due primarily to an approximately 50% increase in binding sites (increased Bmax) versus LXSN cell ECM and of approximately 25% versus LBmutSN cell ECM. These results are consistent with the hypothesis that biglycan, through its glycosaminoglycan side chains, may mediate lipoprotein retention on atherosclerotic plaque ECM.
O'Brien
Kevin D
KD
Division of Cardiology, Box 356422, Department of Medicine, University of Washington, 1959N.E. Pacific St., Seattle, WA 98195-6422, USA. cardiac@u.washington.edu
Lewis
Katherine
K
Fischer
Jens W
JW
Johnson
Pamela
P
Hwang
Jin-Yong
JY
Knopp
Eleanor A
EA
Kinsella
Michael G
MG
Barrett
P Hugh R
PH
Chait
Alan
A
Wight
Thomas N
TN
D000818:Animals; D001161:Arteriosclerosis / Q000378:metabolism*; D058578:Biglycan; D005109:Extracellular Matrix / Q000378:metabolism*; D016326:Extracellular Matrix Proteins; D005786:Gene Expression Regulation; D006801:Humans; D008074:Lipoproteins / Q000378:metabolism*; D009130:Muscle, Smooth / Q000166:cytology* / Q000378:metabolism*; D011509:Proteoglycans / Q000096:biosynthesis*; D051381:Rats
C546884:BGN protein, human; C546886:Bgn protein, rat; D058578:Biglycan; D016326:Extracellular Matrix Proteins; D008074:Lipoproteins; D011509:Proteoglycans