Atorvastatin enhances cellular uptake of oxidized LDL in adipocytes from hypercholesterolemic rabbits.
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.
Zhao
Shui-Ping
SP
Department of Cardiology, The Second XiangYa Hospital of Central South University, 410011, Changsha, PR China
Zhang
Da-Qing
DQ
D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism*; D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000069059:Atorvastatin; D018955:CD36 Antigens / Q000235:genetics; D006538:Heptanoic Acids / Q000494:pharmacology* / Q000627:therapeutic use; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy / Q000378:metabolism*; D007457:Iodine Radioisotopes; D008077:Lipoproteins, LDL / Q000378:metabolism*; D011758:Pyrroles / Q000494:pharmacology* / Q000627:therapeutic use; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011817:Rabbits; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics
D000924:Anticholesteremic Agents; D018955:CD36 Antigens; D006538:Heptanoic Acids; D007457:Iodine Radioisotopes; D008077:Lipoproteins, LDL; D011758:Pyrroles; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; C099252:oxidized low density lipoprotein; D000069059:Atorvastatin