Endothelial bound lipoprotein lipase (LpL) depletion in hypoalbuminemia results from decreased endothelial binding, not decreased secretion.
Hypertriglyceridemia in nephrotic (NS) and Nagase analbuminemic rats (Analb) results from reduced triglyceride clearance. NS and Analb have reduced or absent albumin, reduced plasma oncotic pressure (pi), but Analb lack proteinuria. The heparin releasable lipoprotein lipase (LpL) pool in both models is greatly reduced, suggesting reduced LpL is related to low albumin or pi and not proteinuria. To determine the cause of endothelial LpL reduction, we studied effectors of endothelial LpL (eLpL) levels from gene expression, to delivery and endothelial binding. eLpL was measured as heparin releasable activity. eLpL and secretion rate was measured in isolated hearts perfused with heparin. mRNA levels were measured in rat hearts by kinetic RT-PCR. Finally, binding of (125)I-LpL by competition assays rat endothelial cells measured serum-induced changes in affinity. eLpL in vivo was reduced in nephrotic and Analb rats. While the eLpL pool was reduced in isolated perfused hearts, neither LpL secretion by isolated hearts nor myocardial mRNA was reduced in NS or Analb. Binding of LpL to RAEC preincubated with serum from either NS or Analb was reduced compared to control. LpL mRNA levels and release rate was not altered in hearts from NS rats, while eLpL is depleted, suggesting that reduced eLpL in NS is not the result of reduced delivery. The finding that NS serum alters LpL binding to RAEC suggests LpL depletion results from decreased binding rather than defective delivery. This in turn is a consequence of reduced serum albumin or pi but does not require proteinuria.
Shearer
G C
GC
Department of Veterans Affairs Northern California Health Care System, Mather, California 95616, USA. gcshearer@ucdavis.edu
Kaysen
G A
GA
D000818:Animals; D001011:Aorta / Q000166:cytology / Q000201:enzymology / Q000378:metabolism; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000201:enzymology* / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D034141:Hypoalbuminemia / Q000097:blood / Q000201:enzymology*; D008071:Lipoprotein Lipase / Q000235:genetics / Q000378:metabolism*; D008297:Male; D009206:Myocardium / Q000201:enzymology; D009404:Nephrotic Syndrome / Q000201:enzymology* / Q000503:physiopathology; D011485:Protein Binding; D011507:Proteinuria / Q000201:enzymology / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012709:Serum Albumin / Q000378:metabolism; D014280:Triglycerides / Q000097:blood
D012333:RNA, Messenger; D012709:Serum Albumin; D014280:Triglycerides; D008071:Lipoprotein Lipase