Angiopoietin-like protein 3 (ANGPTL3) deficiency and familial combined hypolipidemia

Three members of the angiopoietin-like(ANGPTL) protein family-ANGPTL3, ANGPTL4 and ANGPTL8-are important regulators of plasma lipoproteins. They inhibit the enzyme lipoprotein lipase, which plays a key role in the intravascular lipolysis of triglycerides present in some lipoprotein classes. This review focuses on the role of ANGPTL3 as emerged from the study of genetic variants of Angptl3 gene in mice and humans. Both loss of function genetic variants and inactivation of Angptl3 gene in mice are associated with a marked reduction of plasma levels of triglyceride and cholesterol and an increased activity of lipoprotein lipase and endothelial lipase. In humans with ANGPTL3 deficiency, caused by homozygous loss of function(LOF) variants of Angptl3 gene, the levels of all plasma lipoproteins are greatly reduced. This plasma lipid disorder referred to as familial combined hypolipidemia(FHBL2) does not appear to be associated with distinct pathological manifestations. Heterozygous carriers of LOF variants have reduced plasma levels of total cholesterol and triglycerides and are at lower risk of developing atherosclerotic cardiovascular disease, as compared to non-carriers. These observations have paved the way to the development of strategies to reduce the plasma level of atherogenic lipoproteins in man by the inactivation of ANGPTL3, using either a specific monoclonal antibody or anti-sense oligonucleotides.

Effect of human angiopoietin-like protein 4 overexpression on the growth of esophageal carcinoma EC9706 cells

Objective： The aim of the study was to construct the eukaryotic expression vector of human angiopoietin-like protein 4 （ANGPTL4） and observe the effect of ANGPTL4 overexpression on the growth of esophageal carcinoma EC9706 cells. Methods： Total RNA was extracted from normal hepatic tissue, and ANGPTL4 cDNA was amplified by RT-PCR. The PCR product was doubly digested by Xbal and Sail, and then recombined into eukaryotic expression vector. Then, plRES-GFP-ANGPTL4 was obtained by G418 selection, then plRES-GFP-ANGPTL4 and plRES-GFP were transfected into EC9706 cells with lipidosome-packaged method. Meanwhile, the transfected cells were selected by G418, and then stable transfected cell lines were obtained. ANGPTL4 mRNA levels, the celt cycles and growth curves of EC9706 cells in experiment group （transfected with plRES-GFP-ANGPTL4）, empty vector group （transfected with plRES-GFP） and blank control group （EC9706 cells without transfection） were detected with RT-PCR, flow cytometry and MTT methods, respectively. Results： Eukaryotic ANGPTL4 expression vector plRES-GFP-ANGPTL4 was successfully constructed. The ANGPTL4 mRNA level （0.21 ± 0.03） in experiment group was significantly higher than that of the empty vector group （0.04 ± 0.008） and the blank control group （0.05 ± 0.007）, with significant differences （P 〈 0.01）. The proportion of cells in S phase in experiment group was significantly different with those of the other two groups （P 〈 0.05）. The cell growth of EC9706 cells in experiment group was slower than those of the other two groups. From the third day, the differences began to be significant. Conclusion： ANGPTL4 overexpression in esophageal carcinoma EC9706 cells could inhibit the growth of EC9706 cells.

PCR-RFLP Polymorphism of ANGPTL4 Gene in Guizhou Yellow Cattle

[ Objective] The paper was to study the genetic effects of ANGPTIA gene in Guizhou yellow cattle. [ Method ] The polymorphisms of ANGPT/A gene in 46 individuals of Guarding yellow cattle and Sinan yellow cattle were detected using PCR-RFLP assay. [Result] A fragment of 260 bp was amplified from AN- GPTIA gene. After digestion by restriction endonuclease MluCl, two genotypes, AA and AB, were produced whereas BB genotype was not found. A mutation of 205T→C was observed through sequencing of different genotypes. AA genotype was dominant in both yellow cattle breeds, and A allele frequency was higher than B allele frequency. X2 test results showed that the two cattle breeds were at Hardy-Weinberg equilibrium state in the digestion site （ P 〉 0.05 ）. [Condusion] The effective molecular markers of Guizbou yellow cattle, such as growth trait and intramuscular fat content, are obtained, which will provide a theoretical basis for mo- lecular breeding of meat performance of Guizhou yellow cattle.

哺乳动物类血管生长因子基因(ANGPTL)的研究进展

类血管生长因子(ANGPTLs)是最新发现的一族与脂类代谢、葡萄糖代谢、血管生成相关的分泌性蛋白质因子.它们对血浆甘油三酯的清除,脂肪组织的脂解以及肥胖症的产生有重要作用.本文主要以AN-GPTL3、ANGPTL4及ANGPTL6基因为代表,对ANGPTLs基因的基本结构、与能量代谢之间的关系和基因表达调控等方面的研究进展进行了综述,对ANGPTLs蛋白应用于治疗肥胖症、高甘油三酯血症以及各种血管病的前景做了展望.

ANGPTL4基因的表达调控及功能研究进展

类血管生长因子4(ANGPTL4)是最新发现的与血管生成、脂类代谢、葡萄糖代谢、肿瘤及代谢性疾病相关的分泌性蛋白质因子。本文从ANGPTL4基因的基本结构、基因表达调控、基因功能及其与肿瘤及代谢性疾病的关系等四个方面对其研究进展进行了综述,并对ANGPTL4蛋白应用于治疗肥胖症、高甘油三酯血症以及各种血管病的前景做了展望。

Protective Effect of Irbesartan by Inhibiting ANGPTL2 Expression in Diabetic Kidney Disease

Angiopoietin-like protein 2(ANGPTL2)stimulates inflammation and is important in the pathogenesis of diabetic kidney disease(DKD).Irbesartan is helpful in reducing diabetes-induced renal damage.In this study,the effects of irbesartan on DKD and its renal protective role involving ANGPTL2 in DKD rats were examined.Wistar rats were divided into normal,DKD,and DKD+irbesartan groups.The DKD+irbesartan group was treated once daily for 8 weeks with 50 mg/kg irbesartan via intragastric gavage.The 24-h urinary albumin was determined each week,renal pathological changes were observed,and expression of ANGPTL2 and nuclear factor-kappa B(NF-κB)in rat renal tissue was assessed by immunohistochemistry.Mouse podocytes cultured in a high concentration of glucose were classified into four groups based on the irbesartan concentrations(0,25,50,and 75ºg/mL).Expression of ANGPTL2 and phosphorylated IκB-αwas assessed by Western blotting.The mRNA levels of ANGPTL2 and monocyte chemotactic protein 1(MCP-1)were assessed by real-time polymerase chain reaction.The DKD rats displayed proteinuria,podocyte injury,and increased ANGPTL2 and NF-κB expression.All were relieved by irbesartan treatment.In podocytes cultured in elevated glucose,ANGPTL2 and phosphorylated IκB-αwere overexpressed at the protein level,and ANGPTL2 and MCP-1 were highly expressed at the mRNA level.Irbesartan down-regulated ANGPTL2 and phosphorylated IκB-αexpression at the protein level and inhibited ANGPTL2 and MCP-1 expression at the mRNA level.The ameliorative effects of irbesartan against DKD involves podocyte protection and suppression of ANGPTL2.