Large HDL particles negatively associate with leukocyte counts independent of cholesterol efflux capacity: A cross sectional study in the population-based LifeLines DEEP cohort
Groenen, Anouk G; Bazioti, Venetia; van Zeventer, Isabelle A; Chen, Lianmin; Groot, Hilde E; Balder, Jan-Willem; Zhernakova, Alexandra; van der Harst, Pim; Rimbert, Antoine; Kuivenhoven, Jan Albert; Fu, Jingyuan; Westerterp, Marit
(2022) Atherosclerosis, volume 343, pp. 20 - 27
(Article)
Abstract
Background and aims: Leukocytosis, the expansion of white blood cells, is associated with increased cardiovascular risk. Studies in animal models have shown that high-density lipoprotein cholesterol (HDL-c) suppresses leukocytosis by mediating cholesterol efflux from hematopoietic stem and progenitor cells. HDL-c showed a moderate negative association with leukocyte numbers in the
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UK Biobank and Multi-Ethnic Study of Atherosclerosis. Cholesterol efflux capacity of HDL (HDL-CEC) or HDL particle (HDL-P) number has been proposed as improved inverse predictor of CVD compared to plasma HDL-c. In the LifeLines DEEP (LLD) cohort (n = 962), a sub-cohort representing the prospective population-based LL cohort from the North of The Netherlands, we tested the hypothesis that HDL-CEC and HDL-P were associated with lower leukocyte counts. Methods: We carried out multivariable regression and causal mediation analyses (CMA) to test associations between HDL-c, HDL-CEC, or HDL-P and leukocyte counts. We measured HDL-CEC in THP-1 macrophages and HDL-P and composition using nuclear magnetic resonance. Results: HDL-c associated negatively with leukocyte counts, as did extra-large and large HDL-P, while HDL-CEC showed no association. Each one-standard deviation (SD) increase in extra-large HDL-P was associated with 3.0% and 4.8% lower leukocytes and neutrophils, respectively (q < 0.001). In contrast, plasma concentration of small HDL-P associated positively with leukocyte and neutrophil counts, as did small HDL-P triglycerides (TG) and total plasma TG. CMA showed that the association between S-HDL-P and leukocytes was mediated by S-HDL-TG. Conclusions: The association between HDL-P and leukocyte counts in the general population is dependent on HDL-P size and composition, but not HDL-CEC.
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Keywords: Atherosclerosis, Composition, HDL, Leukocyte, Lipoprotein, Particle size, Cardiology and Cardiovascular Medicine, Journal Article
ISSN: 0021-9150
Publisher: Elsevier
Note: Funding Information: M. Westerterp is supported by VIDI grant 917.15.350 from the Netherlands Organization of Scientific Research (NWO) , and a Rosalind Franklin Fellowship from the University of Groningen . J. Fu is supported by the Dutch Heart Foundation IN-CONTROL ( CVON2018-27 ), the ERC Consolidator grant (grant agreement No. 101001678), NWO-VICI grant VI.C.202.022 , and the Netherlands Organ-on-Chip Initiative , an NWO Gravitation project ( 024.003.001 ) funded by the Ministry of Education, Culture and Science of the government of The Netherlands. J.A. Kuivenhoven is supported by the Netherlands CardioVascular Research Initiative : ‘the Dutch Heart Foundation , Dutch Federation of University Medical Centers , the Netherlands Organization for Health Research and Development and the Royal Netherlands Academy of Sciences’ ( CVON2017-2020 ; Acronym Genius2). J.A. Kuivenhoven is Established Investigator of the Netherlands Heart Foundation ( 2015T068 ). A. Zhernakova is supported by the Dutch Heart Foundation IN-CONTROL ( CVON2018-27 ), the ERC Starting Grant 715772 , NWO-VIDI grant 016.178.056 , and the NWO Gravitation grant Exposome-NL ( 024.004.017 ). Publisher Copyright: © 2022 The Authors
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