TY - JOUR
T1 - Plasma proteome correlates of lipid and lipoprotein
T2 - Biomarkers of metabolic diversity and inflammation in children of rural Nepal
AU - Lee, Sun Eun
AU - Schulze, Kerry
AU - Stewart, Christine P.
AU - Cole, Robert N.
AU - Wu, Lee S.F.
AU - Eroglu, Abdulkerim
AU - Yager, James D.
AU - Groopman, John
AU - Christian, Parul
AU - West, Keith P.
N1 - Funding Information:
This study was supported by Bill and Melinda Gates Foundation Grants OPP 5241 (Plasma Nutriproteomics Study through the Assessment of Micronutrient Status by Nutriproteomics) and GH 614 (Global Control of Micronutrient Deficiency for the cohort study in Nepal from which plasma samples were obtained). The original field trial in Nepal from 1999 to 2001 in which mothers of studied children were enrolled was supported by United States Agency for International Development Grant HRN-A-00-97-00015-00 (Micronutrients for Health Cooperative Agreement between the Office of Health, Infectious Diseases, and Nutrition and the Center for Human Nutrition, Johns Hopkins Bloomberg School of Public Health). The Sight and Life Global Nutrition Research Institute, Baltimore, MD, and DSM Ltd, Kaiseraugst, Switzerland, provided additional assistance. Author’s Choice—Final version open access under the terms of the Creative Commons CC-BY license. Manuscript received 24 July 2018 and in revised form 25 October 2018. Published, JLR Papers in Press, November 25, 2018 DOI https://doi.org/10.1194/jlr.P088542
Publisher Copyright:
Copyright © 2019 Lee et al.
PY - 2019
Y1 - 2019
N2 - Proteins involved in lipoprotein metabolism can modulate cardiovascular health. While often measured to assess adult metabolic diseases, little is known about the proteomes of lipoproteins and their relation to metabolic dysregulation and underlying inflammation in undernourished child populations. The objective of this population study was to globally characterize plasma proteins systemically associated with HDL, LDL, and triglycerides in 500 Nepalese children. Abnormal lipid profiles characterized by elevated plasma triglycerides and low HDL-cholesterol (HDL-C) concentrations were common, especially in children with subclinical inflammation. Among 982 proteins analyzed, the relative abundance of 11, 12, and 52 plasma proteins was correlated with LDL-cholesterol (r = 0.430.70), triglycerides (r = 0.390.53), and HDL-C (r = 0.490.79) concentrations, respectively. These proteins included apolipoproteins and numerous unexpected intracellular and extracellular matrix binding proteins, likely originating in hepatic and peripheral tissues. Relative abundance of two-thirds of the HDL proteome varied with inflammation, with acute phase reactants higher by 440%, and proteins involved in HDL biosynthesis, cholesterol efflux, vitamin transport, angiogenesis, and tissue repair lower by 320%. Untargeted plasma proteomics detects comprehensive sets of both known and novel lipoprotein-associated proteins likely reflecting systemic regulation of lipoprotein metabolism and vascular homeostasis. Inflammation-altered distributions of the HDL proteome may be predisposing undernourished populations to early chronic disease.
AB - Proteins involved in lipoprotein metabolism can modulate cardiovascular health. While often measured to assess adult metabolic diseases, little is known about the proteomes of lipoproteins and their relation to metabolic dysregulation and underlying inflammation in undernourished child populations. The objective of this population study was to globally characterize plasma proteins systemically associated with HDL, LDL, and triglycerides in 500 Nepalese children. Abnormal lipid profiles characterized by elevated plasma triglycerides and low HDL-cholesterol (HDL-C) concentrations were common, especially in children with subclinical inflammation. Among 982 proteins analyzed, the relative abundance of 11, 12, and 52 plasma proteins was correlated with LDL-cholesterol (r = 0.430.70), triglycerides (r = 0.390.53), and HDL-C (r = 0.490.79) concentrations, respectively. These proteins included apolipoproteins and numerous unexpected intracellular and extracellular matrix binding proteins, likely originating in hepatic and peripheral tissues. Relative abundance of two-thirds of the HDL proteome varied with inflammation, with acute phase reactants higher by 440%, and proteins involved in HDL biosynthesis, cholesterol efflux, vitamin transport, angiogenesis, and tissue repair lower by 320%. Untargeted plasma proteomics detects comprehensive sets of both known and novel lipoprotein-associated proteins likely reflecting systemic regulation of lipoprotein metabolism and vascular homeostasis. Inflammation-altered distributions of the HDL proteome may be predisposing undernourished populations to early chronic disease.
KW - High density lipoprotein-cholesterol
KW - Low density lipoprotein-cholesterol
KW - Plasma proteomics
KW - Triglycerides
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U2 - 10.1194/jlr.P088542
DO - 10.1194/jlr.P088542
M3 - Article
C2 - 30473544
AN - SCOPUS:85059433476
SN - 0022-2275
VL - 60
SP - 149
EP - 160
JO - Journal of Lipid Research
JF - Journal of Lipid Research
IS - 1
ER -