Reference intervals for plasma apolipoprotein A-1 determined with a standardized commercial immunoturbidimetric assay: results from the Framingham Offspring Study

Abstract We have evaluated a commercially available, standardized immunoturbidimetric assay of apolipoprotein (apo) A-I, the major protein constituent of high-density lipoproteins (HDL). We determined the reference ranges of plasma apo A-I concentration for white men and women and related these values to the risk of coronary heart disease (CHD). The mean between-run CV for this assay was 2.9%. As determined with individuals participating cycle 4 of the Framingham Offspring Study, the mean (+/- SD) apo A-I concentration was 13% lower in 1879 men (1.34 +/- 0.23 g/L) than in 1939 women (1.54 +/- 0.28 g/L) (P<0.001). An apo A-I concentration of 1.20 g/L roughly corresponded to the 25th percentile value in men and the 5th percentile in women, and subjects with a concentration below this value were significantly more likely to have CHD than subjects wit a higher concentration (P<0.001).

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Reference intervals for plasma apolipoprotein B determined with a standardized commercial immunoturbidimetric assay: results from the Framingham Offspring Study

Clinical Chemistry ◽

10.1093/clinchem/42.4.515 ◽

1996 ◽

Vol 42 (4) ◽

pp. 515-523 ◽

Cited By ~ 125

Author(s):

J H Contois ◽

J R McNamara ◽

C J Lammi-Keefe ◽

P W Wilson ◽

T Massov ◽

...

Keyword(s):

Low Density Lipoprotein ◽

Density Lipoprotein ◽

B Value ◽

Reference Intervals ◽

Cholesterol Concentration ◽

Reference Ranges ◽

Apo B ◽

Increased Risk ◽

The Mean ◽

Plasma Apolipoprotein

Abstract We evaluated a commercially available, standardized immunoturbidimetric assay for apolipoprotein (apo) B, the protein constituent of low-density lipoprotein (LDL), to establish reference ranges for men and women, and to determine the concentrations associated with increased risk of coronary heart disease (CHD). The between-run CV for assay of a normal-concentration control for this assay was 6.60%. The mean (+/-SD) apo B concentration was 1.03 +/- 0.24 g/L in 1880 men, significantly higher than the mean for 1944 women (0.96 +/- 0.26 g/L) participating in cycle 4 of the Framingham Offspring Study (P<0.001). An apo B value of 1.20 g/L corresponded roughly to the 75th percentile in men, similar to an LDL cholesterol concentration of 1.60 g/L, and subjects with concentrations greater than this were significantly more likely to have CHD than subjects with apo B concentrations less than 1.00 g/L, the approximate 50th percentile (P<0.05 in men and P<0.001 in women).

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Gestational and age-specific cystatin C reference intervals for newborns in China

10.21203/rs.2.19480/v1 ◽

2019 ◽

Author(s):

Chao Tong ◽

Yalan Liu ◽

Yanqiu Wu ◽

Qiong Li ◽

Yipin Wu ◽

...

Keyword(s):

Cystatin C ◽

Newborn Infants ◽

Reference Intervals ◽

Reference Level ◽

Reference Ranges ◽

Perinatal Factors ◽

Blood Cell Count ◽

Serum Cystatin C ◽

Serum Cystatin ◽

The Mean

Abstract Backgroud : To establish reference values of serum cystatin C (CysC) in Chinese newborn infants. Methods: Serum CysC levels were measured in 1919 blood samples from 1044 newborns during their first 28 days of life. CysC levels were analyzed for association between subgroups dichotomized by postnatal age (PA) and gestational age (GA). Reference intervals of serum CysC were determined according to the PA and GA. The association between serum CysC level and other biochemical parameters as well as perinatal factors were also analyzed. Results: In this study, the mean GA was 35.75±2.90 weeks and birth weight was 2613.77±696.72 g. Reference ranges of serum CysC were determined and a general decreasing trend of CysC levels was observed as GA increased. CysC levels differed significantly among the PA and GA groups (P＜0.001). Serum CysC levels were relatively stable throughout GA, except being impacted by white blood cell count within postnatal 24 hours. Moreover, their levels always correlated positively with serum creatinine concentrations (P<0.001). Conclusion: The reference level of serum CysC should be determined according to PA and GA. In contrast to creatinine, serum CysC is a dependable index for assessing renal function in neonate, for there are rare factors influencing it.

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Dietary Mono- and Polyunsaturated Fatty Acids Similarly Increase Plasma Apolipoprotein A-IV Concentrations in Healthy Men and Women

Journal of Nutrition ◽

10.1093/jn/133.6.1821 ◽

2003 ◽

Vol 133 (6) ◽

pp. 1821-1825 ◽

Cited By ~ 11

Author(s):

Mario Kratz ◽

Ursel Wahrburg ◽

Arnold von Eckardstein ◽

Benjie Ezeh ◽

Gerd Assmann ◽

...

Keyword(s):

Fatty Acids ◽

Polyunsaturated Fatty Acids ◽

Men And Women ◽

Healthy Men ◽

Apolipoprotein A ◽

Plasma Apolipoprotein

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Sars-CoV2- infection as a trigger of humoral response against apolipoprotein A-1

European Heart Journal ◽

10.1093/eurheartj/ehab724.2757 ◽

2021 ◽

Vol 42 (Supplement_1) ◽

Author(s):

S Pagano ◽

S Yerly ◽

N Suh ◽

C Le Terrier ◽

L Farrera-Soler ◽

...

Keyword(s):

Public Health ◽

General Population ◽

Molecular Mimicry ◽

Humoral Response ◽

Public Institution ◽

High Density Lipoproteins ◽

Major Protein ◽

Apolipoprotein A ◽

Overall Mortality

Abstract Background Unravelling autoimmune targets triggered by SARS-CoV-2 infection may provide crucial insights in the physiopathology of the disease and foster the development of potential therapeutic candidate targets and prognostic tools. SARS-CoV-2 autoimmune-mediated inflammation have been reported, but the existence of autoantibodies against apolipoprotein A-1 (anti-apoA-1 IgG) in COVID-19 remains unexplored. Anti-apoA-1 IgGs have emerged as an independent biomarker for cardiovascular disease and mortality in humans with proinflammatory and proatherogenic functions in vivo and in vitro. Purpose We want to determine i) the degree of homology between SARS-CoV-2, apoA-1, and Toll-like receptor-2 (TLR2) epitopes, ii) the association between anti-SARSCoV2 and anti-apoA-1 IgGs, and iii) their relationship to prognosis. Methods We performed bioinformatics modelling coupled with mimetic peptides engineering, as well as functional and competition assays with antibodies to identify molecular mimicry between SARS-CoV-2, apoA-1 and TLR2 epitopes. Anti-Spike domain 1 (SD1) IgGs, anti-apoA-1 IgGs and against mimic peptides, as well as cytokines were assessed by immunoassays on a case-control (n=101), an intensive care unit (ICU; n=126) with a 28-days follow-up for overall mortality, and a general population cohort (n=663) with available samples in the pre and post-pandemic period. Results Linear sequence homologies and antibodies cross-reactivity between apoA-1, TLR2, and Spike epitopes were identified. Overall, anti-apoA-1 IgG levels were higher in COVID-19 patients or anti-SARS-CoV-2 seropositive individuals than in healthy donors or anti-SARS-CoV-2 seronegative individuals (p<0.0001). Significant and similar associations were noted between anti-apoA-1, anti-SARS-CoV-2 IgG, cytokines, and lipid profile. In ICU patients, anti-SARS-CoV-2 and anti-apoA-1 seroconversion rates displayed similar 7-days kinetics, reaching 82% for anti-apoA-1 seropositivity. C-statistics (CS) indicated that baseline anti-Spike/TLR2 mimic-peptide IgGs displayed a significant prognostic accuracy for overall mortality at 28 days (CS: 0.64; p=0.02). In the general population, SARS-CoV-2 exposure increased baseline anti-apoA-1 IgG levels. Conclusions COVID-19 induces a marked humoral response against the major protein of high-density lipoproteins. As a correlate of poorer prognosis in other clinical settings, such autoimmunity signatures may relate to long-term COVID-19 prognosis assessment and warrant further scrutiny in the current COVID-19 pandemic. FUNDunding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): This study was funded by the Swiss Federal Office of Public Health, Swiss School of Public Health (Corona Immunitas research program), the Fondation de Bienfaisance du Groupe Pictet, the Fondation Ancrage, the Fondation Privée des HUG, and the Center for Emerging Viral Diseases. The De Reuter (grant Nr 657) and the Schmidheiny Foundation.

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Human apolipoprotein A-I: structure determination and analysis of unusual diffraction characteristics

Acta Crystallographica Section D Biological Crystallography ◽

10.1107/s0907444999013128 ◽

1999 ◽

Vol 55 (12) ◽

pp. 2013-2021 ◽

Cited By ~ 2

Author(s):

David W. Borhani ◽

Jeffrey A. Engler ◽

Christie G. Brouillette

Keyword(s):

Structure Determination ◽

Density Lipoprotein ◽

High Density ◽

High Density Lipoproteins ◽

Major Protein ◽

Data Set ◽

Cholesterol Acyl Transferase ◽

Cell Parameters ◽

Human Apolipoprotein ◽

Apolipoprotein A

The crystallization and structure determination of recombinant human apolipoprotein A-I (apo A-I), the major protein component of high-density lipoprotein, is described. The fragment crystallized, residues 44–243 of native apo A-I [apo Δ(1–43)A-I], is very similar to intact native apo A-I in its ability to bind lipid, to be incorporated into high-density lipoproteins and to activate lecithin–cholesterol acyl transferase. Apo Δ(1–43)A-I crystallizes from 1.0–1.4 M sodium citrate pH 6.5–7.5 in space group P212121, with unit-cell parameters a = 97.47, b = 113.87, c = 196.19 Å (crystal form I). The crystals exhibit unusual diffraction intensity spikes and axial extinctions that are discussed in the context of the 4 Å crystal structure. When flash-cooled to 100 K, the crystals diffract synchrotron radiation to 3 Å resolution. Radiation sensitivity and crystal-to-crystal variation have hindered the assembly of a complete 3 Å data set.

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Apolipoprotein A-I (ApoA-I), Immunity, Inflammation and Cancer

Cancers ◽

10.3390/cancers11081097 ◽

2019 ◽

Vol 11 (8) ◽

pp. 1097 ◽

Cited By ~ 13

Author(s):

Georgila ◽

Vyrla ◽

Drakos

Keyword(s):

Cancer Biology ◽

Animal Studies ◽

High Density Lipoproteins ◽

Major Protein ◽

Multifunctional Protein ◽

Cancer Pathogenesis ◽

Early Cancer Diagnosis ◽

Apolipoprotein A

Apolipoprotein A-I (ApoA-I), the major protein component of high-density lipoproteins (HDL) is a multifunctional protein, involved in cholesterol traffic and inflammatory and immune response regulation. Many studies revealing alterations of ApoA-I during the development and progression of various types of cancer suggest that serum ApoA-I levels may represent a useful biomarker contributing to better estimation of cancer risk, early cancer diagnosis, follow up, and prognosis stratification of cancer patients. In addition, recent in vitro and animal studies disclose a more direct, tumor suppressive role of ApoA-I in cancer pathogenesis, which involves anti-inflammatory and immune-modulatory mechanisms. Herein, we review recent epidemiologic, clinicopathologic, and mechanistic studies investigating the role of ApoA-I in cancer biology, which suggest that enhancing the tumor suppressive activity of ApoA-I may contribute to better cancer prevention and treatment.

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Relation between lipoprotein(a) concentrations in patients with acute-phase response and risk analysis for coronary heart disease

Clinical Chemistry ◽

10.1093/clinchem/43.10.1891 ◽

1997 ◽

Vol 43 (10) ◽

pp. 1891-1895 ◽

Cited By ~ 17

Author(s):

Won-Ki Min ◽

Jae Ok Lee ◽

Jung Won Huh

Keyword(s):

Coronary Heart Disease ◽

Heart Disease ◽

Acute Phase ◽

Acute Phase Response ◽

Sodium Dodecyl ◽

Acute Phase Reactant ◽

Phase Response ◽

Lipoprotein A ◽

Apolipoprotein A ◽

The Mean

Abstract This study investigated whether lipoprotein(a) [Lp(a)] is an acute-phase reactant that can cause important bias in risk factor analysis for coronary heart disease among patients with an acute-phase response (APR patients). To determine whether serum Lp(a) concentrations increase among APR patients, we compared the Lp(a) concentrations and apolipoprotein(a) [apo(a)] phenotypes of 100 controls with those of a random sampling of 100 APR patients. Serum Lp(a) concentration was measured by ELISA; Lp(a) phenotyping was performed by electrophoresis on sodium dodecyl sulfate–polyacrylamide gel. Lp(a) was significantly (P <0.0001) higher among APR patients (mean ± SD 0.300 ± 0.284 g/L) than among controls (0.118 ± 0.193 g/L) even though the distribution of apo(a) phenotypes did not differ significantly. The 100 APR patients were grouped into 4 categories: 48 patients with infections, 25 postoperative patients, 17 patients with tumors, and 10 patients with other diseases, all of whom showed substantially higher Lp(a) values than did the controls. For the S5, S4S5, S5S5, and S4 phenotypes, the mean concentrations of serum Lp(a) were substantially higher among the APR patients.

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The Mechanism of Bisphenol A Atherogenicity Involves Apolipoprotein A-I Downregulation through NF-κB Activation

International Journal of Molecular Sciences ◽

10.3390/ijms20246281 ◽

2019 ◽

Vol 20 (24) ◽

pp. 6281

Author(s):

Violeta G. Trusca ◽

Madalina Dumitrescu ◽

Ioana M. Fenyo ◽

Irina F. Tudorache ◽

Maya Simionescu ◽

...

Keyword(s):

Bisphenol A ◽

Hdl Cholesterol ◽

Dna Interaction ◽

Inhibitory Effect ◽

Environmental Chemicals ◽

High Density Lipoproteins ◽

Major Protein ◽

Dependent Manner ◽

Atherosclerotic Lesions ◽

Apolipoprotein A

Apolipoprotein A-I (apoA-I) is the major protein component of high-density lipoproteins (HDL), mediating many of its atheroprotective properties. Increasing data reveal the pro-atherogenic effects of bisphenol A (BPA), one of the most prevalent environmental chemicals. In this study, we investigated the mechanisms by which BPA exerts pro-atherogenic effects. For this, LDLR−/− mice were fed with a high-fat diet and treated with 50 µg BPA/kg body weight by gavage. After two months of treatment, the area of atherosclerotic lesions in the aorta, triglycerides and total cholesterol levels were significantly increased, while HDL-cholesterol was decreased in BPA-treated LDLR−/− mice as compared to control mice. Real-Time PCR data showed that BPA treatment decreased hepatic apoA-I expression. BPA downregulated the activity of the apoA-I promoter in a dose-dependent manner. This inhibitory effect was mediated by MEKK1/NF-κB signaling pathways. Transfection experiments using apoA-I promoter deletion mutants, chromatin immunoprecipitation, and protein-DNA interaction assays demonstrated that treatment of hepatocytes with BPA induced NF-κB signaling and thus the recruitment of p65/50 proteins to the multiple NF-κB binding sites located in the apoA-I promoter. In conclusion, BPA exerts pro-atherogenic effects downregulating apoA-I by MEKK1 signaling and NF-κB activation in hepatocytes.

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Crystallization of truncated human apolipoprotein A-I in a novel conformation

Acta Crystallographica Section D Biological Crystallography ◽

10.1107/s0907444999008914 ◽

1999 ◽

Vol 55 (9) ◽

pp. 1578-1583 ◽

Cited By ~ 20

Author(s):

David W. Borhani ◽

Jeffrey A. Engler ◽

Christie G. Brouillette

Keyword(s):

Diffraction Limit ◽

Unit Cell ◽

High Density ◽

High Density Lipoproteins ◽

Original Form ◽

Major Protein ◽

Cholesterol Acyl Transferase ◽

Space Group ◽

Human Apolipoprotein ◽

Apolipoprotein A

The crystallization of recombinant human apolipoprotein A-I (apo A-I), the major protein component of high-density lipoprotein, in a new crystal form is described. The fragment crystallized, residues 44–243 of native apo A-I [apo Δ(1–43)A-I], is very similar to intact native apo A-I in its ability to bind lipid, to be incorporated into high-density lipoproteins and to activate lecithin–cholesterol acyl transferase. Apo Δ(1–43)A-I crystallizes, in the presence of β-D-octylglucopyranoside, in space group I222 or I212121, with unit-cell parameters a = 37.11, b = 123.62, c = 164.65 Å and a diffraction limit of 3.2 Å. These form II crystals grow under conditions of significantly lower ionic strength than the original form I crystals (space group P212121, a = 97.47, b = 113.87, c = 196.19 Å, diffraction limit 3.0 Å). Packing arguments show that the unusual open conformation of apo Δ(1–43)A-I found in the form I crystals cannot be packed into the smaller oddly proportioned form II unit cell. Monomeric apo Δ(1–43)A-I, as either a four-helix bundle (∼75 × 30 × 30 Å) or an extended helical rod (∼150 × 20 × 20 Å), can be packed into the form II unit cell. It is concluded, therefore, that apo Δ(1–43)A-I may have crystallized in one of these distinct conformations in the form II crystals.

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Remnant lipoprotein cholesterol and triglyceride reference ranges from the Framingham Heart Study

Clinical Chemistry ◽

10.1093/clinchem/44.6.1224 ◽

1998 ◽

Vol 44 (6) ◽

pp. 1224-1232 ◽

Cited By ~ 69

Author(s):

Judith R McNamara ◽

Paulesh K Shah ◽

Katsuyuki Nakajima ◽

L Adrienne Cupples ◽

Peter W F Wilson ◽

...

Keyword(s):

Coronary Heart Disease ◽

Heart Disease ◽

Premenopausal Women ◽

Reference Ranges ◽

Plasma Samples ◽

Older Individuals ◽

Mean Values ◽

Remnant Lipoprotein ◽

Heart Study ◽

The Mean

Abstract Remnants of triglyceride-rich lipoproteins of both intestinal and liver origin are considered atherogenic, but they have been difficult to isolate and measure. An assay has been developed that allows the measurement of remnant-like particle cholesterol (RLP-C) and triglyceride (RLP-TG). RLP-C and RLP-TG concentrations were measured in >3000 fasting plasma samples obtained from participants in exam cycle 4 of the Framingham Offspring Study and stored at −80 °C. After exclusions, comparisons were made for 2821 samples (1385 women, 1436 men; mean age, 52 years). For women, the mean RLP-C and RLP-TG values were 0.176 ± 0.058 mmol/L (6.8 ± 2.3 mg/dL) and 0.204 ± 0.159 mmol/L (18.1 ± 14.1 mg/dL), respectively; for men, the mean values were 0.208 ± 0.096 mmol/L (8.0 ± 3.7 mg/dL) and 0.301 ± 0.261 mmol/L (26.7 ± 23.1 mg/dL), respectively. Women had significantly lower RLP-C and RLP-TG values (P <0.0001) than men; premenopausal women had significantly lower values than postmenopausal women (P <0.0001); and younger subjects (<50 years) had significantly lower values than older individuals (P <0.0001). The 75th percentile values for RLP-C and RLP-TG were 0.186 mmol/L (7.2 mg/dL) and 0.225 mmol/L (19.9 mg/dL), respectively, for women, and 0.225 mmol/L (8.7 mg/dL) and 0.346 mmol/L (30.6 mg/dL) for men. These data provide reference ranges for use in the evaluation of RLP-C and RLP-TG as potential indicators of risk for coronary heart disease.

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