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Research Article| Volume 140, 155381, March 2023

Relationship between circulating adipokines and cholesterol efflux in subjects with severe carotid atherosclerosis

  • Karina Gasbarrino
    Affiliations
    Division of Experimental Medicine, Department of Medicine, Faculty of Medicine, Research Institute of the McGill University Health Centre, McGill University Montreal, Canada
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  • Anouar Hafiane
    Affiliations
    Division of Experimental Medicine, Department of Medicine, Faculty of Medicine, Research Institute of the McGill University Health Centre, McGill University Montreal, Canada
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  • Ioanna Gianopoulos
    Affiliations
    Division of Experimental Medicine, Department of Medicine, Faculty of Medicine, Research Institute of the McGill University Health Centre, McGill University Montreal, Canada
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  • Huaien Zheng
    Affiliations
    Division of Experimental Medicine, Department of Medicine, Faculty of Medicine, Research Institute of the McGill University Health Centre, McGill University Montreal, Canada
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  • Christos S. Mantzoros
    Affiliations
    Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States

    Section of Endocrinology, Diabetes and Metabolism, Boston VA Healthcare System, Boston, MA, United States
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  • Stella S. Daskalopoulou
    Correspondence
    Corresponding author at: Department of Medicine, Research Institute of the McGill University Health Centre, Glen Site, 1001 Decarie Boulevard, EM1.2230, Montreal, Quebec H4A 3J1, Canada.
    Affiliations
    Division of Experimental Medicine, Department of Medicine, Faculty of Medicine, Research Institute of the McGill University Health Centre, McGill University Montreal, Canada

    Division of Internal Medicine, Department of Medicine, Faculty of Medicine, McGill University Health Centre, McGill University Montreal, Canada
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Published:December 21, 2022DOI:https://doi.org/10.1016/j.metabol.2022.155381

      Highlights

      • CEC is positively associated with total and HMW adiponectin, but not with chemerin or resistin.
      • Total adiponectin had the greatest association accounting for 8.3 % of the variance in CEC.
      • A synergistic interaction between adiponectin and chemerin was observed in raising efflux levels.
      • High CEC was associated with more favourable post-surgical outcomes.

      Abstract

      Aims

      Cholesterol efflux capacity (CEC) as a measure of high-density lipoprotein functionality is independently and inversely associated with increased risk of cardiovascular events and mortality, and advanced plaque morphology. Adipokines, adipose tissue-derived factors, can influence systemic lipoprotein metabolism, and participate in the regulation of vascular function and inflammation. We aimed to investigate the association between CEC and circulating adipokine levels (anti-inflammatory adiponectin, and pro-inflammatory chemerin and resistin) in subjects with severe carotid atherosclerotic disease and evaluate its impact on post-surgical outcomes.

      Methods and results

      This is a cross-sectional study with a 5-year follow-up component. Consecutive patients with severe carotid atherosclerosis scheduled for a carotid endarterectomy were recruited from hospital-based centres in Montreal, Canada (n = 285). Fasting blood samples were collected pre-operatively and used to measure plasma total and high-molecular weight (HMW) adiponectin, chemerin, and resistin, and to perform cholesterol efflux assays in J774 macrophage-like cells. Five-year post-surgery outcomes were obtained through medical chart review. Subjects had a mean age of 70.1 ± 9.4, were 67.0 % male, had various comorbidities (hypercholesterolemia [85.3 %], hypertension [83.5 %], type 2 diabetes [34.5 %], coronary artery disease [38.6 %]), and previously experienced cerebrovascular symptomatology (77.9 %). CEC was independently and positively associated with total and HMW adiponectin levels (ß [95 % confidence interval]; 0.216 [0.134–0.298] and 0.107 [0.037–0.176], respectively) but not with chemerin or resistin. Total adiponectin had the greatest association accounting for 8.3 % of the variance in CEC. Interaction regression models demonstrated a significant interaction between adiponectin and chemerin in increasing CEC. Notably, with each unit increase in CEC there was a 93.9 % decrease in the odds of having an ischemic cerebrovascular event 5 years post-surgery (0.061 [0.007–0.561]).

      Conclusions

      Our findings demonstrated circulating adiponectin to have a strong association with increased CEC in subjects with severe carotid atherosclerosis and high CEC to be associated with more favourable post-surgical outcomes. These findings reflect the importance of adipose tissue health in influencing CEC levels and atherosclerotic cardiovascular disease risk.

      Graphical abstract

      Keywords

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