Dataset Information

Characterization of LP-Z Lipoprotein Particles and Quantification in Subjects with Liver Disease Using a Newly Developed NMR-Based Assay.

ABSTRACT: BACKGROUND:Lipoprotein particles with abnormal compositions, such as lipoprotein X (LP-X) and lipoprotein Z (LP-Z), have been described in cases of obstructive jaundice and cholestasis. The study objectives were to: (1) develop an NMR-based assay for quantification of plasma/serum LP-Z particles, (2) evaluate the assay performance, (3) isolate LP-Z particles and characterize them by lipidomic and proteomic analysis, and (4) quantify LP-Z in subjects with various liver diseases. METHODS:Assay performance was assessed for linearity, sensitivity, and precision. Mass spectroscopy was used to characterize the protein and lipid content of isolated LP-Z particles. RESULTS:The assay showed good linearity and precision (2.5-6.3%). Lipid analyses revealed that LP-Z particles exhibit lower cholesteryl esters and higher free cholesterol, bile acids, acylcarnitines, diacylglycerides, dihexosylceramides, lysophosphatidylcholines, phosphatidylcholines, triacylglycerides, and fatty acids than low-density lipoprotein (LDL) particles. A proteomic analysis revealed that LP-Z have one copy of apolipoprotein B per particle such as LDL, but less apolipoprotein (apo)A-I, apoC3, apoA-IV and apoC2 and more complement C3. LP-Z were not detected in healthy volunteers or subjects with primary biliary cholangitis, primary sclerosing cholangitis, autoimmune hepatitis, or type 2 diabetes. LP-Z were detected in some, but not all, subjects with hypertriglyceridemia, and were high in some subjects with alcoholic liver disease. CONCLUSIONS:LP-Z differ significantly in their lipid and protein content from LDL. Further studies are needed to fully understand the pathophysiological reason for the enhanced presence of LP-Z particles in patients with cholestasis and alcoholic liver disease.

SUBMITTER: Bedi S

PROVIDER: S-EPMC7564541 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Characterization of LP-Z Lipoprotein Particles and Quantification in Subjects with Liver Disease Using a Newly Developed NMR-Based Assay.

Bedi Shimpi S Garcia Erwin E Jeyarajah Elias J EJ Shalaurova Irina I Perez-Matos Maria Camila MC Jiang Z Gordon ZG Dullaart Robin P F RPF Matyus Steven P SP Kirk William J WJ Otvos James D JD Davidson W Sean WS Connelly Margery A MA

Journal of clinical medicine 20200910 9

<h4>Background</h4>Lipoprotein particles with abnormal compositions, such as lipoprotein X (LP-X) and lipoprotein Z (LP-Z), have been described in cases of obstructive jaundice and cholestasis. The study objectives were to: (1) develop an NMR-based assay for quantification of plasma/serum LP-Z particles, (2) evaluate the assay performance, (3) isolate LP-Z particles and characterize them by lipidomic and proteomic analysis, and (4) quantify LP-Z in subjects with various liver diseases.<h4>Method ...[more]

PMID: 32927635

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Project description:BackgroundTo examine the association between lipoprotein(a) (Lp(a)) levels, LPA (rs10455872 and rs3798220) and IL1F9 (rs13415097) single nucleotide polymorphisms (SNPs) with coronary artery calcification (CAC), an important predictor for coronary artery disease (CAD).MethodsWe used data from 3799 (mean age ± SD: 59.0 ± 7.7 years, 47.1% men) Heinz Nixdorf Recall study participants. We applied linear regression models to explore the relation between the log-transformed Lp(a) levels and LPA and IL1F9 SNPs with loge (CAC + 1). The association between the SNPs and log-transformed Lp(a) levels was further assessed using linear regression. The models were adjusted for age and sex (Model 1) and additionally for Lp(a) levels (Model 2).ResultsWe observed a statistically significant association between log-transformed Lp(a) levels and CAC (Model 1: beta per log-unit increase in Lp(a) levels = 0.11; 95% confidence interval [95% CI] [0.04; 0.18], p = 0.002). Furthermore, the LPA SNP rs10455872 showed a statistically significant association with CAC (Model 1: beta per allele = 0.37 [0.14; 0.61], p = 0.002). The association between rs10455872 and CAC was attenuated after adjustment for Lp(a) levels (Model 2: beta per allele = 0.26 [- 0.01; 0.53], p = 0.06). Both LPA SNPs also showed a statistically significant association with Lp(a) levels (Model 1: betars10455872 per allele: 1.56 [1.46; 1.65], p < 0.0001 and betars3798220 per allele: 1.51 [1.33; 1.69], p < 0.0001)). The Mendelian randomization analysis showed that Lp(a) is a causal risk factor for CAC (estimate per log-unit increase in Lp(a) levels (95% CI), p: 0.27 [0.11; 0.44], p = 0.001). The IL1F9 SNP did not show any statistically significant association with Lp(a) levels or with CAC.ConclusionsWe provide evidence for the association of LPA rs10455872 with higher levels of Lp(a) and CAC in our study. The results of our study suggest that rs10455872, mediated by Lp(a) levels, might play a role in promoting the development of atherosclerosis leading to cardiovascular disease events.

Project description:Introduction:Lipoprotein associated phospholipase A2 (Lp-PLA2) has been explored as a potential biomarker for Cardiovascular Disease (CVD). The human Lp-PLA2 is a serine-dependent, Ca2+- independent enzyme. It gives way to oxidised free fatty acids and lysophosphatidyl choline by hydrolysing oxidised phospholipids, that leads to smooth muscle cell apoptosis, inflammatory cell chemotaxis and endothelial cell dysfunction in CVD. Owing to its role in inflammation, it may influence the development and progression of periodontitis as well. Aim:To compare the demographic variables, Gingival Index(GI), Bleeding On Probing (BOP), Probing Pocket Depth (PPD), and Clinical Attachment Level (CAL) with serum lipid profile and Lp-PLA2 level in Chronic Periodontitis (CP) subjects. Materials and Methods:A total of 75 subjects were selected and divided into three groups; based on the inclusion and exclusion criteria: Group I - 25 subjects with severe generalized CP with CAL ? 5 mm in more than 30% of sites. Group II -25 subjects with moderate generalized CD with clinical CAL 3 mm-4 mm in more than 30% of sites. Group III- 25 systemically and periodontally healthy volunteers who served as control. Clinical parameters such as Plaque Index (PI), BOP, Probing Depth (PD) and CAL, lipid profile such as Total Cholesterol (TC), Triglyceride (TG), High density Lipoprotein (HDL), Low Density Lipoprotein (LDL), Very Low Density Lipoprotein (VLDL) as well as Lp-PLA2 were assessed. One-way ANOVA and Tukey's Post-hoc test were used for data analysis. Results:Age was higher in Group I and II when compared to Group III. Group II showed a significant correlation between PI and LDL. In Group III, lower PI was significantly correlated with high HDL and low LDL and BOP was positively correlated with TG and HDL. A significant association of Lp-PLA2 was found to be higher with increase in the TG and VLDL level in Group I and Group II when compared to Group III. Conclusion:The study concluded that Lp-PLA2, TG and VLDL already being a predictor biomarker for atherosclerotic disease can be an inflammatory marker for periodontitis.

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Dataset Information

Characterization of LP-Z Lipoprotein Particles and Quantification in Subjects with Liver Disease Using a Newly Developed NMR-Based Assay.

Publications

Characterization of LP-Z Lipoprotein Particles and Quantification in Subjects with Liver Disease Using a Newly Developed NMR-Based Assay.

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