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Proteomic Determinants of Variation in Cholesterol Efflux : Observations from the Dallas Heart Study

Gangwar, Anamika ; Deodhar, Sneha S. ; Saldanha, Suzanne ; Melander, Olle LU orcid ; Abbasi, Fahim ; Pearce, Ryan W. ; Collier, Timothy S. ; McPhaul, Michael J. ; Furtado, Jeremy D. and Sacks, Frank M. , et al. (2023) In International Journal of Molecular Sciences 24(21).
Abstract

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... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
apolipoprotein, atherosclerotic cardiovascular disease, cholesterol efflux capacity, high-density lipoproteins (HDLs), proteomics
in
International Journal of Molecular Sciences
volume
24
issue
21
article number
15526
publisher
MDPI AG
external identifiers
  • pmid:37958510
  • scopus:85176787611
ISSN
1661-6596
DOI
10.3390/ijms242115526
language
English
LU publication?
yes
id
ae29303c-13e7-4e07-86ba-c6e70216e05e
date added to LUP
2023-12-29 13:20:52
date last changed
2024-04-27 20:24:59
@article{ae29303c-13e7-4e07-86ba-c6e70216e05e,
  abstract     = {{<p>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 &gt;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 (&gt;=90th%) or extremely low CEC (&lt;=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 &lt; 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.</p>}},
  author       = {{Gangwar, Anamika and Deodhar, Sneha S. and Saldanha, Suzanne and Melander, Olle and Abbasi, Fahim and Pearce, Ryan W. and Collier, Timothy S. and McPhaul, Michael J. and Furtado, Jeremy D. and Sacks, Frank M. and Merrill, Nathaniel J. and McDermott, Jason E. and Melchior, John T. and Rohatgi, Anand}},
  issn         = {{1661-6596}},
  keywords     = {{apolipoprotein; atherosclerotic cardiovascular disease; cholesterol efflux capacity; high-density lipoproteins (HDLs); proteomics}},
  language     = {{eng}},
  number       = {{21}},
  publisher    = {{MDPI AG}},
  series       = {{International Journal of Molecular Sciences}},
  title        = {{Proteomic Determinants of Variation in Cholesterol Efflux : Observations from the Dallas Heart Study}},
  url          = {{http://dx.doi.org/10.3390/ijms242115526}},
  doi          = {{10.3390/ijms242115526}},
  volume       = {{24}},
  year         = {{2023}},
}