Abstract
Chronic renal failure (CRF) is associated with premature atherosclerosis, impaired high-density lipoprotein (HDL)-mediated reverse cholesterol transport, depressed clearance, and elevated plasma concentrations of very low-density lipoprotein (VLDL), chylomicrons, and their atherogenic remnants. LDL receptor-related protein (LRP) is a member of the LDL receptor gene family that is heavily expressed in the liver, and mediates removal of at least 30 different ligands, including VLDL remnants (IDL) and chylomicron remnants. This study was conducted to test the hypothesis that the well-known defect in clearance of IDL and chylomicron remnants in CRF may be indicative of diminished hepatic LRP abundance. Hepatic tissue LRP mRNA abundance [reverse transcription-polymerase chain reaction (RT-PCR)] and protein abundance (Western blot analysis) were determined in rats 8 weeks after 5/6 nephrectomy (CRF group) or sham operation (control group). The CRF group exhibited hypertension, diminished creatinine clearance, increased plasma triglyceride concentration, and elevated total cholesterol-to-HDL cholesterol concentration ratio compared to the corresponding values found in the control group. This was associated with a significant down-regulation of hepatic LRP mRNA expression and immunodetectable LRP protein. CRF results in down-regulation of hepatic LRP. This abnormality can, at least in part, account for the previously documented elevation of plasma concentration and depressed clearance of chylomicron remnants and IDL in CRF.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.