Heparin-binding EGF-like growth factor (HB-EGF) antisense oligonucleotide protected against hyperlipidemia-associated atherosclerosis

Background and aims

Heparin-binding EGF-like growth factor (HB-EGF) is a representative EGF family member that interacts with EGFR under diverse stress environment. Previously, we reported that the HB-EGF-targeting using antisense oligonucleotide (ASO) effectively suppressed an aortic aneurysm in the vessel wall and circulatory lipid levels. In this study, we further examined the effects of the HB-EGF ASO administration on the development of hyperlipidemia-associated atherosclerosis using an atherogenic mouse model.

极低密度脂蛋白对HK-2细胞hUAT基因表达的影响

 目的 观察不同浓度极低密度脂蛋白（VLDL）是否调节肾小管上皮细胞（HK-2细胞）人尿酸盐转运子（hUAT）mRNA的表达。方法 根据培养液中所含VLDL浓度的不同，将HK-2细胞分为：①仅使用DMEM/F-12组（对照组）；②DMEM/F-12+ 50 μg/ml VLDL组（V1组）；③DMEM/F-12+100 μg/ml VLDL组（V2组）；④DMEM/F-12+200 μg/ml VLDL组（V3组）；⑤DMEM/F-12+400 μg/ml VLDL组（V4组）。每组均培养 6瓶细胞。上述细胞在不同培养液中分别培养48 h。采用实时荧光定量PCR检测HK-2细胞中hUAT mRNA的相对表达量（2^ΔΔCt法）。结果 所有标本均能检测到hUAT mRNA的表达，但V1～V4组hUAT mRNA表达水平均明显低于对照组，其中，VLDL最低浓度（50 μg/ml）组hUAT mRNA表达水平为对照组的64%，VLDL最高浓度（400 μg/ml）组hUAT mRNA表达水平仅为对照组的24%。结论 VLDL下调hUAT mRNA表达，VLDL的这种作用可能与脂代谢紊乱易合并高尿酸血症有关。     

Polymorphisms at the SRBI locus are associated with lipoprotein levels in subjects with heterozygous familial hypercholesterolemia

Scavenger receptor, class B, type 1 (SRBI) is a promising candidate gene involved in the pathophysiology of atherosclerosis. We have examined the association of three common polymorphisms at the SRBI locus in 77 subjects who were heterozygous for familial hypercholesterolemia (FH). The alleles represented by polymorphisms in exon 1 and exon 8 were associated with variation in plasma concentrations of fasting triglyceride (TG). Mean plasma TG concentrations for homozygotes for the most common allele, and for heterozygotes and homozygotes for the less common allele were 85 +/- 6, 111 +/- 9 and 135 +/- 22 mg/dl (p = 0.011) for exon 1, and 96 +/- 11, 86 +/- 6 and 134 +/- 13 mg/dl (p = 0.007) for exon 8, after adjustment for age, sex and body mass index. In addition, the exon 8 polymorphism was associated with increased total cholesterol (320 +/- 15, 340 +/- 8 and 388 +/- 18 mg/dl, p = 0.015), very low density lipoprotein (VLDL) cholesterol (18 +/- 2.9, 15.7 +/- 1.6 and 33.4 +/- 3.9 mg/dl, p < 0.001) and low density lipoprotein (LDL) cholesterol (251 +/- 15, 270 +/- 8 and 312 +/- 10 mg/dl, p = 0.041) concentrations. In agreement with animal studies, our data also suggest a role for the SRBI in the metabolism of apolipoprotein B (apoB)-containing lipoproteins in humans. This pathway may constitute a backup mechanism to LDL receptor-mediated pathways for the catabolism of these lipoproteins, which could be particularly relevant in subjects with high levels of apoB-containing lipoproteins, such as those occurring in patients with FH.