Native and oxidized low density lipoproteins modulate mesangial cell apoptosis

P Sharma1, K Reddy, N Franki

  • 1Department of Medicine, Long Island Jewish Medical Center, New Hyde Park, New York, USA.

Kidney International
|November 1, 1996
PubMed

Insights

High levels of low-density lipoprotein (LDL) can initially increase mesangial cell proliferation but then induce apoptosis, leading to a hypocellular mesangium in glomerulosclerosis.

Area of Science:

  • Nephrology
  • Cell Biology
  • Cardiovascular Research

Background:

  • Hyperlipidemia is linked to mesangial hypercellularity in glomerulosclerosis.
  • The role of lipids in mesangial cell apoptosis remains unclear.

Purpose of the Study:

  • To investigate if low-density lipoprotein (LDL) can induce mesangial cell apoptosis.
  • To explore the mechanisms behind LDL-induced mesangial cell apoptosis.

Main Methods:

  • In vitro studies using mouse and human mesangial cells.
  • Assessing cell proliferation and apoptosis via cell counts, DNA fragmentation assays, ELISA, and RSG-2 mRNA expression.
  • Measuring thiobarbituric acid reactive species (TBARS) to assess LDL oxidation.
  • Evaluating the effect of superoxide dismutase (SOD) on apoptosis.

Main Results:

  • LDL increased mesangial cell proliferation at lower concentrations and induced apoptosis at higher concentrations.
  • Oxidized LDL (OX-LDL) significantly enhanced mesangial cell apoptosis.
  • LDL-induced apoptosis was mediated by free radical generation, as evidenced by TBARS and attenuation by SOD.
  • Similar effects were observed in human mesangial cells.

Conclusions:

  • LDL has a dual effect on mesangial cells, promoting proliferation and then apoptosis.
  • Oxidation of LDL and free radical generation are key mechanisms in LDL-induced mesangial cell death.
  • These findings suggest LDL contributes to the transition from hypercellular to hypocellular mesangium in glomerulosclerosis.

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