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

J Am Soc Nephrol. 2000 Oct;11(10):1826-1836. doi: 10.1681/ASN.V11101826.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Pressure
  • Body Weight
  • Cells, Cultured
  • Collagen / genetics
  • Gene Expression
  • Glomerulosclerosis, Focal Segmental / complications*
  • Glomerulosclerosis, Focal Segmental / metabolism*
  • Glomerulosclerosis, Focal Segmental / pathology
  • Humans
  • Hypertension / complications*
  • Hypertension / physiopathology
  • Kidney / physiopathology
  • Kidney Glomerulus / pathology
  • Lipids / blood
  • Male
  • Rats
  • Rats, Inbred Dahl / genetics
  • Rats, Inbred Dahl / physiology
  • Rats, Inbred SHR / genetics
  • Rats, Inbred SHR / physiology
  • Receptors, LDL / genetics
  • Receptors, LDL / metabolism*
  • Receptors, Oxidized LDL
  • Scavenger Receptors, Class E
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta1

Substances

  • Lipids
  • OLR1 protein, human
  • OLR1 protein, rat
  • Receptors, LDL
  • Receptors, Oxidized LDL
  • Scavenger Receptors, Class E
  • TGFB1 protein, human
  • Tgfb1 protein, rat
  • Transforming Growth Factor beta
  • Transforming Growth Factor beta1
  • Collagen