Apolipoprotein A-I exchange is impaired in metabolic syndrome patients asymptomatic for diabetes and cardiovascular disease

Mark S. Borja, Bradley Hammerson, Chongren Tang, Olga V. Savinova, Gregory C. Shearer, Michael N. Oda

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Objective: We tested the hypothesis that HDL-apolipoprotein A-I exchange (HAE), a measure of high-density lipoprotein (HDL) function and a key step in reverse cholesterol transport (RCT), is impaired in metabolic syndrome (MetSyn) patients who are asymptomatic for diabetes and cardiovascular disease. We also compared HAE with cell-based cholesterol efflux capacity (CEC) to address previous reports that CEC is enhanced in MetSyn populations. Methods: HAE and ABCA1-specific CEC were measured as tests of HDL function in 60 MetSyn patients and 14 normolipidemic control subjects. Predictors of HAE and CEC were evaluated with multiple linear regression modeling using clinical markers of MetSyn and CVD risk. Results: HAE was significantly reduced in MetSyn patients (49.0 ± 10.9% vs. 61.2 ± 6.1%, P < 0.0001), as was ABCA1-specific CEC (10.1 ± 1.6% vs. 12.3 ± 2.0%, P < 0.002). Multiple linear regression analysis identified apoA-I concentration as a significant positive predictor of HAE, and MetSyn patients had significantly lower HAE per mg/dL of apoA-I (P = 0.004). MetSyn status was a negative predictor of CEC, but triglyceride (TG) was a positive predictor of CEC, with MetSyn patients having higher CEC per mg/dL of TG, but lower overall CEC compared to controls. Conclusions: MetSyn patients have impaired HAE that contributes to reduced capacity for ABCA1-medi-ated CEC. MetSyn status is inversely correlated with CEC but positively correlated with TG, which explains the contradictory results from earlier MetSyn studies focused on CEC. HAE and CEC are inhibited in MetSyn patients over a broad range of absolute apoA-I and HDL particle levels, supporting the observation that this patient population bears significant residual cardiovascular disease risk.

Original languageEnglish (US)
Article numbere0182217
JournalPloS one
Volume12
Issue number8
DOIs
StatePublished - Aug 2017

Fingerprint

apolipoprotein A-I
Asymptomatic Diseases
Apolipoprotein A-I
metabolic syndrome
Medical problems
cardiovascular diseases
diabetes
Cardiovascular Diseases
Cholesterol
cholesterol
high density lipoprotein
HDL Lipoproteins
Triglycerides
triacylglycerols
Linear regression
Linear Models
Regression analysis

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Borja, Mark S. ; Hammerson, Bradley ; Tang, Chongren ; Savinova, Olga V. ; Shearer, Gregory C. ; Oda, Michael N. / Apolipoprotein A-I exchange is impaired in metabolic syndrome patients asymptomatic for diabetes and cardiovascular disease. In: PloS one. 2017 ; Vol. 12, No. 8.
@article{4438fd7e32764ba793a23bb5066cfa1f,
title = "Apolipoprotein A-I exchange is impaired in metabolic syndrome patients asymptomatic for diabetes and cardiovascular disease",
abstract = "Objective: We tested the hypothesis that HDL-apolipoprotein A-I exchange (HAE), a measure of high-density lipoprotein (HDL) function and a key step in reverse cholesterol transport (RCT), is impaired in metabolic syndrome (MetSyn) patients who are asymptomatic for diabetes and cardiovascular disease. We also compared HAE with cell-based cholesterol efflux capacity (CEC) to address previous reports that CEC is enhanced in MetSyn populations. Methods: HAE and ABCA1-specific CEC were measured as tests of HDL function in 60 MetSyn patients and 14 normolipidemic control subjects. Predictors of HAE and CEC were evaluated with multiple linear regression modeling using clinical markers of MetSyn and CVD risk. Results: HAE was significantly reduced in MetSyn patients (49.0 ± 10.9{\%} vs. 61.2 ± 6.1{\%}, P < 0.0001), as was ABCA1-specific CEC (10.1 ± 1.6{\%} vs. 12.3 ± 2.0{\%}, P < 0.002). Multiple linear regression analysis identified apoA-I concentration as a significant positive predictor of HAE, and MetSyn patients had significantly lower HAE per mg/dL of apoA-I (P = 0.004). MetSyn status was a negative predictor of CEC, but triglyceride (TG) was a positive predictor of CEC, with MetSyn patients having higher CEC per mg/dL of TG, but lower overall CEC compared to controls. Conclusions: MetSyn patients have impaired HAE that contributes to reduced capacity for ABCA1-medi-ated CEC. MetSyn status is inversely correlated with CEC but positively correlated with TG, which explains the contradictory results from earlier MetSyn studies focused on CEC. HAE and CEC are inhibited in MetSyn patients over a broad range of absolute apoA-I and HDL particle levels, supporting the observation that this patient population bears significant residual cardiovascular disease risk.",
author = "Borja, {Mark S.} and Bradley Hammerson and Chongren Tang and Savinova, {Olga V.} and Shearer, {Gregory C.} and Oda, {Michael N.}",
year = "2017",
month = "8",
doi = "10.1371/journal.pone.0182217",
language = "English (US)",
volume = "12",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "8",

}

Apolipoprotein A-I exchange is impaired in metabolic syndrome patients asymptomatic for diabetes and cardiovascular disease. / Borja, Mark S.; Hammerson, Bradley; Tang, Chongren; Savinova, Olga V.; Shearer, Gregory C.; Oda, Michael N.

In: PloS one, Vol. 12, No. 8, e0182217, 08.2017.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Apolipoprotein A-I exchange is impaired in metabolic syndrome patients asymptomatic for diabetes and cardiovascular disease

AU - Borja, Mark S.

AU - Hammerson, Bradley

AU - Tang, Chongren

AU - Savinova, Olga V.

AU - Shearer, Gregory C.

AU - Oda, Michael N.

PY - 2017/8

Y1 - 2017/8

N2 - Objective: We tested the hypothesis that HDL-apolipoprotein A-I exchange (HAE), a measure of high-density lipoprotein (HDL) function and a key step in reverse cholesterol transport (RCT), is impaired in metabolic syndrome (MetSyn) patients who are asymptomatic for diabetes and cardiovascular disease. We also compared HAE with cell-based cholesterol efflux capacity (CEC) to address previous reports that CEC is enhanced in MetSyn populations. Methods: HAE and ABCA1-specific CEC were measured as tests of HDL function in 60 MetSyn patients and 14 normolipidemic control subjects. Predictors of HAE and CEC were evaluated with multiple linear regression modeling using clinical markers of MetSyn and CVD risk. Results: HAE was significantly reduced in MetSyn patients (49.0 ± 10.9% vs. 61.2 ± 6.1%, P < 0.0001), as was ABCA1-specific CEC (10.1 ± 1.6% vs. 12.3 ± 2.0%, P < 0.002). Multiple linear regression analysis identified apoA-I concentration as a significant positive predictor of HAE, and MetSyn patients had significantly lower HAE per mg/dL of apoA-I (P = 0.004). MetSyn status was a negative predictor of CEC, but triglyceride (TG) was a positive predictor of CEC, with MetSyn patients having higher CEC per mg/dL of TG, but lower overall CEC compared to controls. Conclusions: MetSyn patients have impaired HAE that contributes to reduced capacity for ABCA1-medi-ated CEC. MetSyn status is inversely correlated with CEC but positively correlated with TG, which explains the contradictory results from earlier MetSyn studies focused on CEC. HAE and CEC are inhibited in MetSyn patients over a broad range of absolute apoA-I and HDL particle levels, supporting the observation that this patient population bears significant residual cardiovascular disease risk.

AB - Objective: We tested the hypothesis that HDL-apolipoprotein A-I exchange (HAE), a measure of high-density lipoprotein (HDL) function and a key step in reverse cholesterol transport (RCT), is impaired in metabolic syndrome (MetSyn) patients who are asymptomatic for diabetes and cardiovascular disease. We also compared HAE with cell-based cholesterol efflux capacity (CEC) to address previous reports that CEC is enhanced in MetSyn populations. Methods: HAE and ABCA1-specific CEC were measured as tests of HDL function in 60 MetSyn patients and 14 normolipidemic control subjects. Predictors of HAE and CEC were evaluated with multiple linear regression modeling using clinical markers of MetSyn and CVD risk. Results: HAE was significantly reduced in MetSyn patients (49.0 ± 10.9% vs. 61.2 ± 6.1%, P < 0.0001), as was ABCA1-specific CEC (10.1 ± 1.6% vs. 12.3 ± 2.0%, P < 0.002). Multiple linear regression analysis identified apoA-I concentration as a significant positive predictor of HAE, and MetSyn patients had significantly lower HAE per mg/dL of apoA-I (P = 0.004). MetSyn status was a negative predictor of CEC, but triglyceride (TG) was a positive predictor of CEC, with MetSyn patients having higher CEC per mg/dL of TG, but lower overall CEC compared to controls. Conclusions: MetSyn patients have impaired HAE that contributes to reduced capacity for ABCA1-medi-ated CEC. MetSyn status is inversely correlated with CEC but positively correlated with TG, which explains the contradictory results from earlier MetSyn studies focused on CEC. HAE and CEC are inhibited in MetSyn patients over a broad range of absolute apoA-I and HDL particle levels, supporting the observation that this patient population bears significant residual cardiovascular disease risk.

UR - http://www.scopus.com/inward/record.url?scp=85026676079&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85026676079&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0182217

DO - 10.1371/journal.pone.0182217

M3 - Article

C2 - 28767713

AN - SCOPUS:85026676079

VL - 12

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 8

M1 - e0182217

ER -