TY - JOUR
T1 - Diabetes enhances lectin-like oxidized LDL receptor-1 (LOX-1) expression in the vascular endothelium
T2 - Possible role of LOX-1 ligand and AGE
AU - Chen, Mingyi
AU - Nagase, Miki
AU - Fujita, Toshiro
AU - Narumiya, Shuh
AU - Masaki, Tomoh
AU - Sawamura, Tatsuya
N1 - Funding Information:
We thank Japan Tobacco Inc. for technical assistance in raising the monoclonal antibody, JTX20 used in this study. This work was supported in part by grants from the Ministry of Education, Culture, Sports, Science and Technology of Japan; the Ministry of Health, Labour and Welfare of Japan, the Organization for Pharmaceutical Safety and Research, Takeda Science Foundation, and the Ono Medical Research Foundation.
PY - 2001/10/5
Y1 - 2001/10/5
N2 - Diabetes mellitus accelerating atherosclerosis was associated with the enhanced glycoxidative modification of lipoproteins. LOX-1, the endothelial oxidized LDL receptor might be involved in the pathogenesis of diabetic atherosclerosis. In this study, we examined the vascular expression of LOX-1 in streptozotocin-induced diabetic rats. We found that LOX-1 was significantly increased in diabetic rat aorta compared with nondiabetic control. Immunohistochemistry revealed that the most distinctive staining of LOX-1 was in the endothelial cells, especially in the bifurcations of artery branches from aorta. In cultured aortic endothelial cells, diabetic rat serum and advanced glycation endproducts-BSA induced LOX-1 expression, while control rat serum along with high glucose did not. Applying a competitive inhibition assay, we found that LOX-1 ligand activity was accumulated in the diabetic rat serum, mainly in VLDL/LDL fractions. In addition, VLDL/LDL prominently increased LOX-1 among all the lipoprotein fractions of diabetic rat serum. In conclusion, diabetes markedly upregulated LOX-1 expression in the aortic endothelial cells. The enhanced glycoxidative modification of lipoproteins may contribute to the underlying mechanisms.
AB - Diabetes mellitus accelerating atherosclerosis was associated with the enhanced glycoxidative modification of lipoproteins. LOX-1, the endothelial oxidized LDL receptor might be involved in the pathogenesis of diabetic atherosclerosis. In this study, we examined the vascular expression of LOX-1 in streptozotocin-induced diabetic rats. We found that LOX-1 was significantly increased in diabetic rat aorta compared with nondiabetic control. Immunohistochemistry revealed that the most distinctive staining of LOX-1 was in the endothelial cells, especially in the bifurcations of artery branches from aorta. In cultured aortic endothelial cells, diabetic rat serum and advanced glycation endproducts-BSA induced LOX-1 expression, while control rat serum along with high glucose did not. Applying a competitive inhibition assay, we found that LOX-1 ligand activity was accumulated in the diabetic rat serum, mainly in VLDL/LDL fractions. In addition, VLDL/LDL prominently increased LOX-1 among all the lipoprotein fractions of diabetic rat serum. In conclusion, diabetes markedly upregulated LOX-1 expression in the aortic endothelial cells. The enhanced glycoxidative modification of lipoproteins may contribute to the underlying mechanisms.
KW - Advanced glycation endproducts
KW - Atherosclerosis
KW - Diabetes mellitus
KW - Endothelium
KW - LOX-1
KW - OxLDL
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U2 - 10.1006/bbrc.2001.5674
DO - 10.1006/bbrc.2001.5674
M3 - Article
C2 - 11573959
AN - SCOPUS:0035812691
SN - 0006-291X
VL - 287
SP - 962
EP - 968
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 4
ER -