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Hepatic HDL receptor, SR-B1 and Apo A-I expression in chronic renal failure
1Department of Medicine, University of California, Irvine, Orange 92868, USA.
Insights
Chronic renal failure (CRF) down-regulates hepatic apolipoprotein A-I (Apo A-I) gene expression, lowering plasma Apo A-I. The HDL receptor remains unaffected in CRF rats, and parathyroidectomy does not alter these expressions.
Area of Science:
- Nephrology
- Cardiovascular Science
- Molecular Biology
Background:
- Chronic renal failure (CRF) is linked to dyslipidemia, including hypertriglyceridemia and reduced high-density lipoprotein (HDL)-cholesterol and apolipoprotein A-I (Apo A-I).
- Uremic hypertriglyceridemia may stem from lipase deficiencies influenced by excess parathyroid hormone (PTH).
- This study investigates if CRF impacts HDL composition and concentration via altered hepatic expression of Apo A-I or the HDL receptor.
Purpose of the Study:
- To test if chronic renal failure (CRF) dysregulates hepatic expression of apolipoprotein A-I (Apo A-I) and/or the HDL receptor.
- To determine the effect of parathyroidectomy (PTx) on these expressions in CRF.
Main Methods:
- Quantified hepatic Apo A-I and HDL receptor mRNA using Northern blot in CRF rats, parathyroidectomized CRF rats (CRF-PTx), and controls.
- Assessed HDL receptor protein mass via Western blot in the same groups.
- Utilized a 5/6 nephrectomy model to induce CRF in rats.
Main Results:
- CRF rats showed reduced hepatic Apo A-I mRNA abundance.
- Hepatic HDL receptor mRNA and protein levels were normal in CRF rats.
- Parathyroidectomy (PTx) did not alter hepatic Apo A-I mRNA, HDL receptor mRNA, or HDL receptor protein abundance in CRF rats.
Conclusions:
- CRF leads to down-regulation of hepatic Apo A-I gene expression, explaining reduced plasma Apo A-I concentrations.
- CRF does not impact hepatic HDL receptor mRNA or protein expression in this rat model.
- Parathyroidectomy had no discernible effect on Apo A-I or HDL receptor expression in CRF rats.
Background:
Chronic renal failure (CRF) is associated with hypertriglyceridaemia and depressed plasma high-density lipoprotein (HDL)-cholesterol and apolipoprotein A-I (Apo A-I) concentrations. Uraemic hypertriglyceridaemia is due, in part, to lipoprotein lipase and hepatic lipase deficiencies, which are causally linked to excess parathormone (PTH). This study was designed to test the hypothesis that depressed plasma concentration and abnormal composition of HDL in CRF may be due to dysregulation of hepatic expression of Apo A-I and/or the newly discovered HDL receptor.
Methods:
Hepatic Apo A-I and HDL receptor mRNA abundance (Northern blot), and HDL receptor protein mass (Western blot) were determined in CRF rats (5/6 nephrectomy), parathyroidectomized CRF rats (CRF-PTx) and sham-operated controls.
Results:
The CRF group exhibited normal hepatic HDL receptor mRNA and HDL receptor protein abundance coupled with reduced hepatic Apo A-I mRNA. Hepatic Apo A-I mRNA, HDL receptor mRNA and protein abundance were not affected by PTx.
Conclusions:
CRF results in the down-regulation of hepatic Apo A-I gene expression, which accounts for the known reduction in plasma Apo A-I concentration. However, CRF does not affect HDL receptor mRNA or protein expression in this model. Neither Apo A-I nor HDL receptor expression were modified by PTx in CRF rats.