Atorvastatin enhances cellular uptake of oxidized LDL in adipocytes from hypercholesterolemic rabbits

Clin Chim Acta. 2004 Jan;339(1-2):189-94. doi: 10.1016/j.cccn.2003.10.007.

Abstract

Background: Peroxisome proliferator-activated receptor gamma (PPARgamma) and CD36, a plausible pathway for the oxidized low-density lipoprotein (ox-LDL) uptake in monocytes, is highly expressed in adipocytes. Few studies have explored the cellular uptake of ox-LDL in adipocytes and its significance on atherosclerosis.

Methods: Rabbits on high-cholesterol diets were randomly assigned to either 1.5 mg/kg/day atorvastatin (n = 5) or starch (n = 5) for 2 weeks. Subcutaneous adipose tissues were collected for adipocytes culture. The uptake of 125I-OxLDL in adipocytes was determined by a gamma-counter and each sample was normalized to protein concentration. Reverse transcription polymerase chain reaction (RT-PCR) was used to evaluate PPARgamma and CD36 mRNA expressions.

Results: Adipocytes took up 125I-OxLDL in a concentration-dependent manner. Two weeks of atorvastatin treatment enhanced the cellular uptake of 125I-OxLDL, which was closely related to the reduced plasma low-density lipoprotein cholesterol (LDL-C) concentrations and increased mRNA expressions of PPARgamma and CD36 in adipocytes, respectively.

Conclusions: Adipocytes may be a potential pool for plasma ox-LDL, and atorvastatin can improve the ox-LDL uptake in adipocytes possibly through reducing cholesterol concentration and upregulating mRNA expressions of PPARgamma and CD36.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes / drug effects*
  • Adipocytes / metabolism*
  • Animals
  • Anticholesteremic Agents / pharmacology*
  • Anticholesteremic Agents / therapeutic use
  • Atorvastatin
  • CD36 Antigens / genetics
  • Heptanoic Acids / pharmacology*
  • Heptanoic Acids / therapeutic use
  • Hypercholesterolemia / blood
  • Hypercholesterolemia / drug therapy
  • Hypercholesterolemia / metabolism*
  • Iodine Radioisotopes
  • Lipoproteins, LDL / metabolism*
  • Pyrroles / pharmacology*
  • Pyrroles / therapeutic use
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rabbits
  • Receptors, Cytoplasmic and Nuclear / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transcription Factors / genetics

Substances

  • Anticholesteremic Agents
  • CD36 Antigens
  • Heptanoic Acids
  • Iodine Radioisotopes
  • Lipoproteins, LDL
  • Pyrroles
  • RNA, Messenger
  • Receptors, Cytoplasmic and Nuclear
  • Transcription Factors
  • oxidized low density lipoprotein
  • Atorvastatin