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Correlation between liver and monocyte expression of the LDL receptor and HMG‐CoA reductase in guinea pigs
Author(s) -
Aggarwal Dimple,
Freake Hedley C,
Soliman Ghada A,
Dutta Amrita,
Fernandez MariaLuz
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.lb82
Subject(s) - hmg coa reductase , reductase , endocrinology , medicine , biology , ldl receptor , monocyte , cholesterol , receptor , lipoprotein , enzyme , biochemistry
HMG‐CoA reductase and the LDL receptor are ubiquitously expressed in major tissues. Since the liver plays a major role in regulating circulating LDL, the effects of drug or dietary interventions on these proteins are usually measured in liver. In humans, monocytes are used as a surrogate for liver to assess regulation of these genes, although there is concern regarding data interpretation. We evaluated the relationship between liver and monocyte expression of these regulatory genes of cholesterol synthesis and plasma LDL in guinea pigs, a well established model for human cholesterol and lipoprotein metabolism. RNA was extracted from liver and monocytes of 30 guinea pigs (10/group) treated with 0, low (0.08 mg/d) or high (0.85 mg/d) rapamycin (RAPA), an mTOR inhibitor. Using reverse transcriptase‐PCR, we determined LDL receptor and HMG‐CoA reductase mRNA abundance. RAPA treatment did not alter the expression of these genes. This observation was consistent with similar plasma LDL cholesterol between RAPA‐treated and control guinea pigs. The relative values for monocyte HMG‐CoA reductase expression were 2.61 ± 2.33, 1.95 ± 1.85 and 1.39 ± 1.52 for control, low and high RAPA groups, respectively while the corresponding values for the liver were 1.54 ± 1.90, 0.81 ± 0.91 and 0.77 ± 1.04. A positive correlation was found between liver and monocytes for both HMG‐CoA reductase (r=0.613, P < 0.0001) and the LDL receptor (r = 0.595, P < 0.005). 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 [Supported in part by NIH grant KO1 DK60654 warded to GS]