Proteinuria and plasma compositional changes contribute to defective lipoprotein catabolism in the nephrotic syndrome by separate mechanisms.
Triglyceride (TG)-rich lipoproteins are primarily increased in the nephrotic syndrome (NS) as a result of decreased catabolism. Lipoprotein lipase (LpL) is the rate limiting enzyme for lipolysis of TG. The biologically active endothelial bound LpL pool is reduced in NS providing one mechanism for decreased clearance of very low density lipoprotein (VLDL). LpL, however, is also reduced in the Nagase Analbuminemic Rat (NAR) to the same extent as in NS, suggesting that other factors contribute to decreased VLDL clearance. Hyperlipidemia worsens with the onset of proteinuria and is reduced when proteinuria abates. We established that while VLDL from NS rats bind poorly to bovine aortic endothelial cells (BAEC) in the presence of saturating LpL while, VLDL from NAR bind more avidly than control. We then established that rat aortic endothelial cells (RAEC) incubated with serum from NAR or from NS rats bind significantly less exogenous LpL. Thus decreased clearance of VLDL in NS results from: 1) reduced endothelial bound LpL; an effect of serum from animals with reduced oncotic pressure (pi) that makes cells unable to bind LpL; and 2) an alteration in VLDL binding to endothelial bound LpL. The former has no relationship to proteinuria while the latter occurs as a consequence of proteinuria. These effects combine to suppress VLDL clearance.
Shearer
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GC
Division of Nephrology, Department of Medicine, University of California Davis, Davis, USA.
Kaysen
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D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D002417:Cattle; D002478:Cells, Cultured; D003470:Culture Media / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D007457:Iodine Radioisotopes; D008055:Lipids / Q000097:blood*; D008071:Lipoprotein Lipase / Q000378:metabolism; D008074:Lipoproteins / Q000378:metabolism*; D008079:Lipoproteins, VLDL / Q000378:metabolism; D008297:Male; D009404:Nephrotic Syndrome / Q000378:metabolism*; D011485:Protein Binding; D011507:Proteinuria / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012709:Serum Albumin / Q000378:metabolism
D003470:Culture Media; D007457:Iodine Radioisotopes; D008055:Lipids; D008074:Lipoproteins; D008079:Lipoproteins, VLDL; D012709:Serum Albumin; D008071:Lipoprotein Lipase