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Acquired VLDL receptor deficiency in experimental nephrosis

1997; Elsevier BV; Volume: 51; Issue: 6 Linguagem: Inglês

10.1038/ki.1997.242

1523-1755

Kaihui Liang, Nosratola D. Vaziri,

Protein Kinase Regulation and GTPase Signaling

Nephrotic syndrome (NS) is commonly associated with elevation of plasma very low density lipoprotein (VLDL) and triglyceride concentrations. VLDL receptor (VLDL-R) is a novel protein that specifically binds and internalizes VLDL particles and is primarily distributed in heart, skeletal muscle, brain and adipose tissue. Based on these properties, VLDL-R is thought to play a role in VLDL and triglyceride metabolism. The present study was undertaken to test the hypothesis that elevation of plasma VLDL in NS may be, in part, related to VLDL-R deficiency. To this end, heart and skeletal muscle VLDL-R protein (Western blot) and mRNA (Northern blot) were measured at various points in the course of puromycin-induced NS in rats. The results were compared with those obtained in the placebo-treated normal control animals. The NS group showed a significant decline in VLDL-R protein (relative to total plasma membrane protein mass) in the heart and skeletal muscle paralleling the rise in plasma VLDL and triglyceride concentrations. The fall in VLDL-R protein was accompanied by a parallel decline in VLDL-R mRNA in the heart but not skeletal muscle. VLDL-R protein was directly related to proteinuria and inversely related to plasma VLDL and triglyceride concentrations. In conclusion, puromycin-induced NS in rats is associated with profound reduction in heart and skeletal muscle VLDL receptor protein. Acquired VLDL-R deficiency, shown for the first time here, may contribute to elevation of plasma concentration of triglyceride-rich VLDL in the nephrotic rat. Recognition of this abnormality reveals another dimension of the complex dysregulation of lipid metabolism in NS. The precise mechanism responsible for NS-induced VLDL-R deficiency in this model is not clear and awaits further investigation.