Validation of using gene expression in mononuclear cells as a marker for hepatic cholesterol metabolism

Dimple Aggarwal, Hedley C. Freake, Ghada Soliman, Amrita Dutta, Maria Luz Fernandez

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

HMG-CoA reductase and the LDL receptor are ubiquitously expressed in major tissues. Since the liver plays a major role in regulating circulating LDL, it is usually of interest to measure the effects of drug or dietary interventions on these proteins in liver. In humans, peripheral blood mononuclear cells have been used as a surrogate for liver to assess regulation of these genes, although there is concern regarding the validity of this approach. The purpose of this study was to evaluate the relationship between liver and mononuclear cell expression of HMG-CoA reductase and the LDL receptor in guinea pigs, a well established model for human cholesterol and lipoprotein metabolism. We extracted RNA from liver and mononuclear cells of guinea pigs from a previous study where the effects of rapamycin, an immunosuppresant drug used for transplant patients, on lipid metabolism were evaluated. Guinea pigs were assigned to three different diets containing the same amount of fat (15 g/100 g) and cholesterol (0.08 g/100 g) for a period of 3 weeks. The only difference among diets was the concentration of rapamycin: 0, 0.0028 or 0.028 g/100 g. There were no differences in plasma LDL cholesterol (LDL-C) among groups. Values were 78.4 ± 14.3, 65.8 ± 17.2 and 68.4 ± 45.4 mg/dL (P > 0.05) for guinea pigs treated with 0, low or high doses of rapamycin, respectively. The mRNA abundance for the LDL receptor and HMG-CoA reductase was measured both in liver (n = 30) and mononuclear cells (n = 22) using reverse transcriptase PCR. In agreement with the finding of no changes in plasma LDL-C, there were also no differences for the expression of HMG-CoA reductase or the LDL receptor among groups. However, a positive correlation was found between liver and mononuclear cells for both HMG-CoA reductase (r = 0.613, P < 0.01) and the LDL receptor (r = 0.622, P < 0.01). These correlations suggest that monocytes can be used in humans as an index for liver to assess diet and drug effects on the expression of HMG-CoA reductase and the LDL receptor.

Original languageEnglish (US)
Article number22
JournalLipids in Health and Disease
Volume5
DOIs
StatePublished - Aug 15 2006

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Hydroxymethylglutaryl CoA Reductases
Metabolism
Gene expression
Liver
LDL Receptors
Cholesterol
Gene Expression
Guinea Pigs
Sirolimus
Nutrition
Diet
LDL Cholesterol
Pharmaceutical Preparations
Plasmas
Transplants
RNA-Directed DNA Polymerase
Reverse Transcriptase Polymerase Chain Reaction
Lipid Metabolism
Monocytes
Blood Cells

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

Cite this

Validation of using gene expression in mononuclear cells as a marker for hepatic cholesterol metabolism. / Aggarwal, Dimple; Freake, Hedley C.; Soliman, Ghada; Dutta, Amrita; Fernandez, Maria Luz.

In: Lipids in Health and Disease, Vol. 5, 22, 15.08.2006.

Research output: Contribution to journalArticle

Aggarwal, Dimple ; Freake, Hedley C. ; Soliman, Ghada ; Dutta, Amrita ; Fernandez, Maria Luz. / Validation of using gene expression in mononuclear cells as a marker for hepatic cholesterol metabolism. In: Lipids in Health and Disease. 2006 ; Vol. 5.
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