ANGPLT3 Impacts Not Only Proteinuria But Also Hyperlipidemia in Nephrotic Syndrome

Abstract Background: Why primary nephrotic syndrome (PNS) patients often accompany with dyslipidemia is unknown. Recent studies discovered that angiopoietin-like protein 3 (ANGPTL3) is an important regulator in lipid metabolism. In this study, we explored how ANGPTL3 impact dyslipidemia in PNS development. Methods: We detected the expression serum level of ANGPTL3 in PNS patients. Further, degree of proteinuria and lipid metabolism were tested in angptl3 overexpression-transgenic (angptl3-tg) mice at different weeks of age. Meanwhile, this study used CRISP/Cas 9 system to build angptl3-knockout (angptl3-/-) mice to observe LPS-treated nephrotic mice. Results: There was a significant correlation between the expression level of serum ANGPTL3 and the level of cholesterol, triglyceride and low density lipoprotein in PNS patients. Along with the age growing, the angptl3-tg mice emerged more and more severe hypertriglyceridemia and proteinuria. The pathological features showed rich lipid droplets deposition of hepatocytes and diffuse podocytes effacement with these angptl3-tg mice. Compared to wild type mice, angptl3-/- mice showed significant less degree of lipid dysfunction and proteinuria after treated with LPS. The ANGPTL3’ effects on nephrotic dyslipidemia was confirmed in the cultured hepatocyte with knock-down or overexpressed angptl3. Finally, the significant alters of lipoprotein lipase (LPL) were tested in liver tissues between Angptl3-/- and wild type mice with LPS treatment. Conclusion: ANGPTL3 could be involved in development of dyslipidemia, besides proteinuria in PNS pathogenesis. Inhibiting LPL expression is a reason why ANGPTL3 induce hyperlipidemia in PNS.