Expression of LOX-1, an oxidized low-density lipoprotein receptor, in experimental hypertensive glomerulosclerosis.
Oxidized low-density lipoprotein (OxLDL) has been implicated in atherosclerosis and glomerulosclerosis. LOX-1 is a recently identified OxLDL receptor that is abundantly expressed in vascular endothelial cells. The aim of the present study was to investigate LOX-1 expression in the kidneys of hypertensive rats. Dahl salt-sensitive (DS) and salt-resistant (DR) rats were fed a 0.3% or 8% NaCl diet. Some DS 8% rats were treated with manidipine or hydralazine. LOX-1 gene expression was markedly elevated in the kidneys and glomeruli of hypertensive DS 8% rats compared with those of normotensive DR and DS 0.3% rats. Prolonged salt loading further increased the renal LOX-1 expression in DS rats. The LOX-1 upregulation in DS 8% rats was accompanied by renal overexpression of transforming growth factor-beta 1 and type I collagen, impaired renal function, and histologic glomerulosclerotic changes, all of which were ameliorated by antihypertensive treatment. LOX-1 was indeed expressed in the glomeruli in vivo and in cultured glomerular cells in vitro. However, LOX-1 expression was elevated in the aorta but not the kidneys of spontaneously hypertensive rats, which exhibited hypertension but minor glomerulosclerotic changes. In conclusion, the LOX-1 upregulation in the kidney of DS 8% rats was parallel to glomerulosclerotic changes and renal dysfunction, suggesting a possible pathogenetic role for renal LOX-1 in the progression to hypertensive glomerulosclerosis.
Nagase
Miki
M
Fourth Department of Internal Medicine, University of Tokyo School of Medicine, Tokyo, Japan.
Kaname
Shinya
S
Fourth Department of Internal Medicine, University of Tokyo School of Medicine, Tokyo, Japan.
Nagase
Takashi
T
Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
Wang
Gang
G
Fourth Department of Internal Medicine, University of Tokyo School of Medicine, Tokyo, Japan.
Ando
Katsuyuki
K
Fourth Department of Internal Medicine, University of Tokyo School of Medicine, Tokyo, Japan.
Sawamura
Tatsuya
T
Department of Bioscience, National Cardiovascular Center Research Institute, Suita, Osaka, Japan.
Fujita
Toshiro
T
Fourth Department of Internal Medicine, University of Tokyo School of Medicine, Tokyo, Japan.
D000818:Animals; D001794:Blood Pressure; D001835:Body Weight; D002478:Cells, Cultured; D003094:Collagen / Q000235:genetics; D015870:Gene Expression; D005923:Glomerulosclerosis, Focal Segmental / Q000150:complications* / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D006973:Hypertension / Q000150:complications* / Q000503:physiopathology; D007668:Kidney / Q000503:physiopathology; D007678:Kidney Glomerulus / Q000473:pathology; D008055:Lipids / Q000097:blood; D008297:Male; D051381:Rats; D020303:Rats, Inbred Dahl / Q000235:genetics / Q000502:physiology; D011918:Rats, Inbred SHR / Q000235:genetics / Q000502:physiology; D011973:Receptors, LDL / Q000235:genetics / Q000378:metabolism*; D051131:Receptors, Oxidized LDL; D051127:Scavenger Receptors, Class E; D016212:Transforming Growth Factor beta / Q000235:genetics; D053773:Transforming Growth Factor beta1
D008055:Lipids; C495137:OLR1 protein, human; C495136:OLR1 protein, rat; D011973:Receptors, LDL; D051131:Receptors, Oxidized LDL; D051127:Scavenger Receptors, Class E; C508960:TGFB1 protein, human; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D003094:Collagen