Potential function of angiopoietin-like protein 3 in hyperlipidemia of nephrotic syndrome

Abstract

Objective To explore whether angiopoietin-like protein 3 (Angptl3) is involved in the development of hyperlipidemia in nephrotic syndrome. Methods PCR analysis was carried out to identify the genotypes of Angptl3 Knockout mice. Sixty newborn Angptl3 knockout (KO) mice and wild type (WT) mice were randomly divided into four groups: KO-ADR, KO-Saline, WT-ADR and WT-Saline group. In each group 6 mice at different time points were separately analyzed: the pre-molding, molding 1st, 2nd, 4th, 8th week. WT-ADR and KO-ADR groups were treated with 25 mg/kg ADR once via tail vein injection at day 0; WT-saline and KO-saline groups were injected with the same volume of saline. Automatic biochemical analyzer was employed to test serum cholesterol (Cho) and triglycerides (TG) levels, ELISA method to detect the urine protein and urine creatinine, and real-time fluorescence quantitative PCR to detect the expression of Angptl3 mRNA in the renal tissue. Results (1)There were no significant differences in the weight, morphology or function of the liver and kidney between the KO and WT mice. Compared with WT mice, the levels of Cho and TG obviously decreased in the KO mice (P <0.01). (2) In the WT-ADR group, urinary protein levels and the levels of Cho and TG increased significantly at 1st week after ADR injection (P <0.05), while serum albumin level decreased dramatically (P <0.05). The serum levels of Cho and TG increased gradually during the entire study period. The expressions of Angptl3 mRNA in kidney tissues were up-regulated significantly from 1st week (P<0.05) to 8th weeks(P <0.01). Furthermore, the expression of Angptl3 mRNA was significantly positively correlated with the Cho and TG levels (r=0.885,P <0.01;r=0.788,P <0.01, respectively). (3)The levels of Cho and TG in the Angptl3-/- mice were lower than those in the WT mice during the entire study period after ADR injection (P <0.05). Conclusions Angptl3 is involved in the development of hyperlipidemia in nephrotic syndrome. Knocking-out of Angptl3 may play an anti-dyslipidemic role in nephrotic syndrome. Key words: Doxorubicin; Nephrotic syndrome; Hyperlipidemia; Angiopoietin-like protein 3