Hepatic HDL receptor, SR-B1 and Apo A-I expression in chronic renal failure.
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.
Vaziri
N D
ND
Department of Medicine, University of California, Irvine, Orange 92868, USA.
Deng
G
G
Liang
K
K
D000818:Animals; D016632:Apolipoprotein A-I / Q000235:genetics*; D002352:Carrier Proteins; D005786:Gene Expression Regulation; D007676:Kidney Failure, Chronic / Q000378:metabolism*; D008075:Lipoproteins, HDL; D008099:Liver / Q000378:metabolism*; D008297:Male; D016105:Parathyroidectomy; D012333:RNA, Messenger / Q000032:analysis; D016601:RNA-Binding Proteins; D051381:Rats; D017207:Rats, Sprague-Dawley; D018110:Receptors, Lipoprotein / Q000235:genetics*
D016632:Apolipoprotein A-I; D002352:Carrier Proteins; D008075:Lipoproteins, HDL; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D018110:Receptors, Lipoprotein; C031616:high density lipoprotein receptors; C075197:high density lipoprotein binding protein