The Analysis of Human Serum Albumin Proteoforms Using Compositional Framework

Sinari, Shripad; Nedelkov, Dobrin; Reaven, Peter D.; Billheimer, Dean

doi:10.1007/978-3-319-45809-0_8

Cited by 2 publications

(1 citation statement)

References 29 publications

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“…When examined in the multivariate models, apo CIII proteoform composition was expressed as additive natural log-ratios (ALR) of less abundant proteoforms to the most abundant CIII 1 to allow accurate estimation of relationships among variables that sum to a constant value as occurs with compositional data. 34,35 Covariates were chosen for their known prior association with apo CIII proteoforms or study outcomes. Pearson correlations were used to describe the associations between total plasma apo CIII concentration and percentages of individual proteoforms.…”

Section: Statistical Analysesmentioning

confidence: 99%

Apo CIII Proteoforms, Plasma Lipids, and Cardiovascular Risk in MESA

Sinari

Koska

Hu³

et al. 2023

ATVB

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Background: ApoC-III is an important regulator of triglyceride metabolism and was associated with cardiovascular risk in several cohorts. ApoC-III is present in 4 major proteoforms, a native peptide (C-III 0a ), and glycosylated proteoforms with zero (C-III 0b ), 1 (C-III 1 , most abundant), or 2 (C-III 2 ) sialic acids, which may differentially modify lipoprotein metabolism. We studied the relationships of these proteoforms with plasma lipids and cardiovascular risk. Methods: ApoC-III proteoforms were measured by mass spectrometry immunoassay in baseline plasma samples of 5791 participants of Multi-Ethnic Study of Atherosclerosis, an observational community-based cohort. Standard plasma lipids were collected for up to 16 years and cardiovascular events (myocardial infarction, resuscitated cardiac arrest, or stroke) were adjudicated for up to 17 years. Results: ApoC-III proteoform composition differed by age, gender, race and ethnicity, body mass index, and fasting glucose. Notably, C-III 1 was lower in older participants, men and Blacks and Chinese (versus Whites), and higher in obesity and diabetes. In contrast, C-III 2 was higher in older participants, men, Blacks, and Chinese, and lower in Hispanics and obesity. Higher C-III 2 to C-III 1 ratio (C-III 2 /III 1 ) was associated with lower triglycerides and higher HDL (high-density lipoprotein) in cross-sectional and longitudinal models, independently of clinical and demographic risk factors and total apoC-III. The associations of C-III 0a /III 1 and C-III 0b /III 1 with plasma lipids were weaker and varied through cross-sectional and longitudinal analyses. Total apoC-III and C-III 2 /III 1 were positively associated with cardiovascular disease risk (n=669 events, hazard ratios, 1.14 [95% CI, 1.04–1.25] and 1.21 [1.11–1.31], respectively); however, the associations were attenuated after adjustment for clinical and demographic characteristics (1.07 [0.98–1.16]; 1.07 [0.97–1.17]). In contrast, C-III 0b /III 1 was inversely associated with cardiovascular disease risk even after full adjustment including plasma lipids (0.86 [0.79–0.93]). Conclusions: Our data indicate differences in clinical and demographic relationships of apoC-III proteoforms, and highlight the importance of apoC-III proteoform composition in predicting future lipid patterns and cardiovascular disease risk.

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Section: Statistical Analysesmentioning

confidence: 99%