Expression of LOX-1, an oxidized low-density lipoprotein receptor, in experimental hypertensive glomerulosclerosis

Oxidized low-density lipoprotein (OxLDL) has been implicated in atheroscler osis 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 hyperte nsive 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 hyd ralazine. LOX-1 gene expression was markedly elevated in the kidneys and gl omeruli of hypertensive DS 8% rats compared with those of normotensive DR a nd DS 0.3% rats. Prolonged salt loading further increased the renal LOX-1 e xpression 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 col lagen, impaired renal function, and histologic glomerulosclerotic changes, all of which were ameliorated by antihypertensive treatment. LOX-1 was inde ed expressed in the glomeruli in vivo and in cultured glomerular cells in v itro. However, LOX-1 expression was elevated in the aorta but not the kidne ys of spontaneously hypertensive rats, which exhibited hypertension but min or 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.