Automated immunoturbidimetric analysis of six plasma apolipoproteins: Correlation with radial immunodiffusion assays

Ikeda, Teruaki; Shibuya, Yohko; Senba, Umeko; Sugiuchi, Hiroyuki; Araki, Shukuro; Uji, Yukitaka; Okabe, Hiroaki

doi:10.1002/jcla.1860050204

Cited by 100 publications

(42 citation statements)

References 17 publications

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“…It is also worth noting that the level of each plasma protein in these transgenic mice is similar to that found in humans. [23][24][25] Previous data indicate that human ApoCIII levels range from 10 to 50 mg/dL, which is similar to the 15 mg/dL found in our transgenic mice. [23][24][25] Furthermore, we find human ApoAV levels are Ϸ0.005 to 0.05 mg/dL (manuscript in preparation), similar to the Ϸ0.025 mg/dL found in our APOA1/C3/A4/A5 BAC transgenic mice.…”

Section: Discussionsupporting

confidence: 84%

Analysis of Apolipoprotein A5, C3, and Plasma Triglyceride Concentrations in Genetically Engineered Mice

Baroukh

Baugé

Akiyama

et al. 2004

ATVB

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Objective-Both the apolipoprotein A5 and C3 genes have repeatedly been shown to play an important role in determining plasma triglyceride concentrations in humans and mice. In mice, transgenic and knockout experiments indicate that plasma triglyceride levels are strongly altered by changes in the expression of either of these 2 genes. In humans, common polymorphisms in both genes have also been associated with plasma triglyceride concentrations. These similar findings raised the issue of the relationship between these 2 genes and altered triglycerides. Methods and Results-To address this issue, we generated independent lines of mice that either overexpressed ("double transgenic") or completely lacked ("double knockout") both apolipoprotein genes. We report that both "double transgenic" and "double knockout" mice display normal triglyceride concentrations compared with overexpression or deletion of either gene alone. Furthermore, we find that human ApoAV plasma protein levels in the "double transgenic" mice are Ϸ500-fold lower than human ApoCIII levels, supporting ApoAV as a potent triglyceride modulator despite its low concentration. Conclusions-Together, these data support that APOA5 and APOC3 independently influence plasma triglyceride concentrations but in an opposing manner. Key Words: apolipoprotein Ⅲ triglyceride Ⅲ transgenic mice A polipoproteins constitute a class of polypeptides found on plasma lipoprotein particles that play an important role in lipid transport and metabolism. Alterations in the level or structure of these molecules have been shown to dramatically impact plasma lipid concentrations and, in many cases, atherosclerosis susceptibility in humans as well as in mice. In mammals, evidence exists that some of the apolipoprotein family members are evolutionarily related as the result of gene duplication events. For instance, apolipoprotein AI, AIV, and E all share amino acid identity and similarity, supportive of a common ancestral origin. 1 We recently identified an additional member of this apolipoprotein family, named ApoAV, through the use of human-mouse genomic sequence comparisons. 2 APOA5 is located within the welldescribed APOA1/A4/C3 gene cluster on human chromosome 11q23. 3 Although APOA5 is most closely related to APOA4, manipulations of APOA5 levels in mice resulted in profound effects on plasma triglyceride concentrations, a phenotype not present in APOA4 mouse models. 2,4,5 APOA5 transgenic mice displayed significantly reduced (Ϫ70%) triglyceride concentrations whereas apoA5 knockouts had an increase (ϩ400%) in this lipid parameter. 2 Further genetic studies in humans have consistently reported strong association between common APOA5 polymorphisms and plasma triglyceride concentrations. 2,6 -11 In addition to APOA5, the neighboring APOC3 gene has also been reported to have a striking effect on human and mouse plasma triglyceride concentrations. However, APOC3 has an opposite impact on triglycerides, with transgenic mice having increased concentrations (ϩ200% to 2000%) and knocko...

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Section: Discussionsupporting

confidence: 84%

Analysis of Apolipoprotein A5, C3, and Plasma Triglyceride Concentrations in Genetically Engineered Mice

Baroukh

Baugé

Akiyama

et al. 2004

ATVB

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“…The levels of total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL) and total triglyceride in plasma were measured enzymatically. 12,13 We analyzed the concentrations of high-sensitivity C-reactive protein (CRP) using the Behring Latex-Enhanced CRP assay on the Behring Nephelometer Analyzer System (Dade, Behring). The concentrations of IL-6 were measured by chemiluminescent enzyme immunoassay.…”

Section: Adipocytokines Inflammatory Markers Lipid Concentrations mentioning

confidence: 99%

Adipocytokines and endothelial function in preeclamptic women

et al. 2010

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Visceral fat accumulation stimulates the production of adipocytokines in patients with metabolic syndrome. Excess body weight gain during pregnancy is a risk factor for preeclampsia. To evaluate whether the pathogenesis of preeclampsia is similar to that of metabolic syndrome, we measured plasma adipocytokine concentrations and investigated the association between plasma adiponectin concentrations and body weight gain or endothelial function in preeclamptic women. We investigated 15 preeclamptic and 17 women with uncomplicated pregnancies. Women with preeclampsia had significantly lower plasma concentrations of adiponectin (10.2 ± 2.0 vs. 7.3 ± 2.2 lg ml À1 , Po0.01), but higher concentrations of leptin, plasminogen activator inhibitor-1, interleukin-6, vascular cell adhesion molecule-1, E-selectin and C-reactive protein. Plasma triglyceride levels were significantly higher in preeclamptic patients, but the levels of other lipids did not differ significantly between the two groups. We found that flow-mediated vasodilation was significantly decreased in preeclamptic women compared with controls (10.6 ± 6.4 vs. 3.8 ± 2.0%, Po0.001). Plasma adiponectin concentrations correlated negatively with body mass index (r¼À0.50, Po0.05) and body weight gain during pregnancy (r¼À0.63, Po0.01), and positively with flow-mediated vasodilation (r¼0.50, Po0.05) in preeclamptic women, but not in women with uncomplicated pregnancies. Similar to the patients with metabolic syndrome, we found that dysregulation of adipocytokines, such as low adiponectin levels and high levels of other adipocytokines, and excess body weight gain during pregnancy, may decrease plasma adiponectin concentrations that are associated with endothelial dysfunction in preeclamptic women.

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“…The LDL cholesterol was calculated by subtraction with the Friedewald algorithm (Friedewald et al, 1972). The concentration of the serum apo A-I and B (Ikeda et al, 1991) was determined with a modified, commercially available turbidimetric assay (Apo A-I Auto Á N and Apo B Auto Á N; Daiichi Pure Chemicals Co., Tokyo, Japan). The fatty acid composition of the serum cholesterol esters, phospholipids and triacylglycerols was determined according to the methods previously described (Ikeda et al, 1998).…”

Section: Measurementsmentioning

confidence: 99%

Serum lipid profiles in Japanese women and men during consumption of walnuts

et al. 2002

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Objective: To determine the serum cholesterol, apolipoproteins and LDL oxidizability in young Japanese women and men during walnut consumption and to evaluate its active principle. Design: Experimental study with a randomized design. Subjects: Twenty healthy women and 20 healthy men. Interventions: Subjects were randomly assigned to consume each of two mixed natural diets for 4 weeks in a cross-over design. Reference and walnut diets were designed and the walnut diet had 12.5% of the energy derived from walnuts (44 -58 g=day). Results: The total cholesterol and serum apolipoprotein B concentrations, and the ratio of LDL cholesterol to HDL cholesterol was significantly lowered in women and men when fed on the walnut diet, than when on the reference diet (P 0.05). The LDL cholesterol concentration was significantly lowered in women on the walnut diet (0.22 mmol=l, P ¼ 0.0008), whereas this decrease was not significant in men (0.18 mmol=l, P ¼ 0.078). The most prominent change in the fatty acid composition of the cholesteryl esters from serum after the walnut diet was an elevation of a-linolenic acid in women (76%, P < 0.001) and men (107%, P < 0.001). This elevation was negatively correlated to the change in LDL cholesterol in women (r ¼ 0.496, P ¼ 0.019) and men (r ¼ 0.326, P ¼ 0.138). The LDL oxidizability in women was not influenced by the diets (P ¼ 0.19). Conclusions: a-Linolenic acid in the walnut diet appears to be responsible for the lowering of LDL cholesterol in women.

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Automated immunoturbidimetric analysis of six plasma apolipoproteins: Correlation with radial immunodiffusion assays

Cited by 100 publications

References 17 publications

Analysis of Apolipoprotein A5, C3, and Plasma Triglyceride Concentrations in Genetically Engineered Mice

Analysis of Apolipoprotein A5, C3, and Plasma Triglyceride Concentrations in Genetically Engineered Mice

Adipocytokines and endothelial function in preeclamptic women

Serum lipid profiles in Japanese women and men during consumption of walnuts

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