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Proteomic Determinants of Variation in Cholesterol Efflux: Observations from the Dallas Heart Study
High-density lipoproteins (HDLs) are promising targets for predicting and treating atherosclerotic cardiovascular disease (ASCVD), as they mediate removal of excess cholesterol from lipid-laden macrophages that accumulate in the vasculature. This functional property of HDLs, termed cholesterol efflu...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10648649/ https://www.ncbi.nlm.nih.gov/pubmed/37958510 http://dx.doi.org/10.3390/ijms242115526 |
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author | Gangwar, Anamika Deodhar, Sneha S. Saldanha, Suzanne Melander, Olle Abbasi, Fahim Pearce, Ryan W. Collier, Timothy S. McPhaul, Michael J. Furtado, Jeremy D. Sacks, Frank M. Merrill, Nathaniel J. McDermott, Jason E. Melchior, John T. Rohatgi, Anand |
author_facet | Gangwar, Anamika Deodhar, Sneha S. Saldanha, Suzanne Melander, Olle Abbasi, Fahim Pearce, Ryan W. Collier, Timothy S. McPhaul, Michael J. Furtado, Jeremy D. Sacks, Frank M. Merrill, Nathaniel J. McDermott, Jason E. Melchior, John T. Rohatgi, Anand |
author_sort | Gangwar, Anamika |
collection | PubMed |
description | High-density lipoproteins (HDLs) are promising targets for predicting and treating atherosclerotic cardiovascular disease (ASCVD), as they mediate removal of excess cholesterol from lipid-laden macrophages that accumulate in the vasculature. This functional property of HDLs, termed cholesterol efflux capacity (CEC), is inversely associated with ASCVD. HDLs are compositionally diverse, associating with >250 different proteins, but their relative contribution to CEC remains poorly understood. Our goal was to identify and define key HDL-associated proteins that modulate CEC in humans. The proteomic signature of plasma HDL was quantified in 36 individuals in the multi-ethnic population-based Dallas Heart Study (DHS) cohort that exhibited persistent extremely high (>=90th%) or extremely low CEC (<=10th%) over 15 years. Levels of apolipoprotein (Apo)A-I associated ApoC-II, ApoC-III, and ApoA-IV were differentially correlated with CEC in high (r = 0.49, 0.41, and −0.21 respectively) and low (r = −0.46, −0.41, and 0.66 respectively) CEC groups (p for heterogeneity (pHet) = 0.03, 0.04, and 0.003 respectively). Further, we observed that levels of ApoA-I with ApoC-III, complement C3 (CO3), ApoE, and plasminogen (PLMG) were inversely associated with CEC in individuals within the low CEC group (r = −0.11 to −0.25 for subspecies with these proteins vs. r = 0.58 to 0.65 for subspecies lacking these proteins; p < 0.05 for heterogeneity). These findings suggest that enrichment of specific proteins on HDLs and, thus, different subspecies of HDLs, differentially modulate the removal of cholesterol from the vasculature. |
format | Online Article Text |
id | pubmed-10648649 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-106486492023-10-24 Proteomic Determinants of Variation in Cholesterol Efflux: Observations from the Dallas Heart Study Gangwar, Anamika Deodhar, Sneha S. Saldanha, Suzanne Melander, Olle Abbasi, Fahim Pearce, Ryan W. Collier, Timothy S. McPhaul, Michael J. Furtado, Jeremy D. Sacks, Frank M. Merrill, Nathaniel J. McDermott, Jason E. Melchior, John T. Rohatgi, Anand Int J Mol Sci Article High-density lipoproteins (HDLs) are promising targets for predicting and treating atherosclerotic cardiovascular disease (ASCVD), as they mediate removal of excess cholesterol from lipid-laden macrophages that accumulate in the vasculature. This functional property of HDLs, termed cholesterol efflux capacity (CEC), is inversely associated with ASCVD. HDLs are compositionally diverse, associating with >250 different proteins, but their relative contribution to CEC remains poorly understood. Our goal was to identify and define key HDL-associated proteins that modulate CEC in humans. The proteomic signature of plasma HDL was quantified in 36 individuals in the multi-ethnic population-based Dallas Heart Study (DHS) cohort that exhibited persistent extremely high (>=90th%) or extremely low CEC (<=10th%) over 15 years. Levels of apolipoprotein (Apo)A-I associated ApoC-II, ApoC-III, and ApoA-IV were differentially correlated with CEC in high (r = 0.49, 0.41, and −0.21 respectively) and low (r = −0.46, −0.41, and 0.66 respectively) CEC groups (p for heterogeneity (pHet) = 0.03, 0.04, and 0.003 respectively). Further, we observed that levels of ApoA-I with ApoC-III, complement C3 (CO3), ApoE, and plasminogen (PLMG) were inversely associated with CEC in individuals within the low CEC group (r = −0.11 to −0.25 for subspecies with these proteins vs. r = 0.58 to 0.65 for subspecies lacking these proteins; p < 0.05 for heterogeneity). These findings suggest that enrichment of specific proteins on HDLs and, thus, different subspecies of HDLs, differentially modulate the removal of cholesterol from the vasculature. MDPI 2023-10-24 /pmc/articles/PMC10648649/ /pubmed/37958510 http://dx.doi.org/10.3390/ijms242115526 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Gangwar, Anamika Deodhar, Sneha S. Saldanha, Suzanne Melander, Olle Abbasi, Fahim Pearce, Ryan W. Collier, Timothy S. McPhaul, Michael J. Furtado, Jeremy D. Sacks, Frank M. Merrill, Nathaniel J. McDermott, Jason E. Melchior, John T. Rohatgi, Anand Proteomic Determinants of Variation in Cholesterol Efflux: Observations from the Dallas Heart Study |
title | Proteomic Determinants of Variation in Cholesterol Efflux: Observations from the Dallas Heart Study |
title_full | Proteomic Determinants of Variation in Cholesterol Efflux: Observations from the Dallas Heart Study |
title_fullStr | Proteomic Determinants of Variation in Cholesterol Efflux: Observations from the Dallas Heart Study |
title_full_unstemmed | Proteomic Determinants of Variation in Cholesterol Efflux: Observations from the Dallas Heart Study |
title_short | Proteomic Determinants of Variation in Cholesterol Efflux: Observations from the Dallas Heart Study |
title_sort | proteomic determinants of variation in cholesterol efflux: observations from the dallas heart study |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10648649/ https://www.ncbi.nlm.nih.gov/pubmed/37958510 http://dx.doi.org/10.3390/ijms242115526 |
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