Apolipoprotein(a) production and clearance are associated with plasma IL-6 and IL-18 levels, dependent on ethnicity.

APO(a) isoform size APO(a) kinetics ASCVD Inflammation Lipoprotein(a)

Journal

Atherosclerosis
ISSN: 1879-1484
Titre abrégé: Atherosclerosis
Pays: Ireland
ID NLM: 0242543

Informations de publication

Date de publication:
13 Feb 2024
Historique:
received: 19 09 2023
revised: 31 01 2024
accepted: 01 02 2024
medline: 2 3 2024
pubmed: 2 3 2024
entrez: 1 3 2024
Statut: aheadofprint

Résumé

High plasma lipoprotein (a) [Lp(a)] levels are associated with increased atherosclerotic cardiovascular disease (ASCVD), in part attributed to elevated inflammation. High plasma Lp(a) levels inversely correlate with apolipoprotein (a) [(APO(a)] isoform size. APO(a) isoform size is negatively associated with APO(a) production rate (PR) and positively associated with APO(a) fractional catabolic rate (FCR). We asked whether APO(a) PR and FCR (kinetics) are associated with plasma levels of interleukin (IL)-6 and IL-18, pro-inflammatory interleukins that promote ASCVD. We used samples from existing data of APO(a) kinetic studies from an ethnically diverse cohort (n = 25: 10 Black, 9 Hispanic, and 6 White subjects) and assessed IL-6 and IL-18 plasma levels. We performed multivariate linear regression analyses to examine the relationships between predictors APO(a) PR or APO(a) FCR, and outcome variables IL-6 or IL-18. In these analyses, we adjusted for parameters known to affect Lp(a) levels and APO(a) PR and FCR, including race/ethnicity and APO(a) isoform size. APO(a) PR and FCR were positively associated with plasma IL-6, independent of isoform size, and dependent on race/ethnicity. APO(a) PR was positively associated with plasma IL-18, independent of isoform size and race/ethnicity. APO(a) FCR was not associated with plasma IL-18. Our studies demonstrate a relationship between APO(a) PR and FCR and plasma IL-6 or IL-18, interleukins that promote ASCVD. These studies provide new insights into Lp(a) pro-inflammatory properties and are especially relevant in view of therapies targeting APO(a) to decrease cardiovascular risk.

Sections du résumé

BACKGROUND AND AIMS OBJECTIVE
High plasma lipoprotein (a) [Lp(a)] levels are associated with increased atherosclerotic cardiovascular disease (ASCVD), in part attributed to elevated inflammation. High plasma Lp(a) levels inversely correlate with apolipoprotein (a) [(APO(a)] isoform size. APO(a) isoform size is negatively associated with APO(a) production rate (PR) and positively associated with APO(a) fractional catabolic rate (FCR). We asked whether APO(a) PR and FCR (kinetics) are associated with plasma levels of interleukin (IL)-6 and IL-18, pro-inflammatory interleukins that promote ASCVD.
METHODS METHODS
We used samples from existing data of APO(a) kinetic studies from an ethnically diverse cohort (n = 25: 10 Black, 9 Hispanic, and 6 White subjects) and assessed IL-6 and IL-18 plasma levels. We performed multivariate linear regression analyses to examine the relationships between predictors APO(a) PR or APO(a) FCR, and outcome variables IL-6 or IL-18. In these analyses, we adjusted for parameters known to affect Lp(a) levels and APO(a) PR and FCR, including race/ethnicity and APO(a) isoform size.
RESULTS RESULTS
APO(a) PR and FCR were positively associated with plasma IL-6, independent of isoform size, and dependent on race/ethnicity. APO(a) PR was positively associated with plasma IL-18, independent of isoform size and race/ethnicity. APO(a) FCR was not associated with plasma IL-18.
CONCLUSIONS CONCLUSIONS
Our studies demonstrate a relationship between APO(a) PR and FCR and plasma IL-6 or IL-18, interleukins that promote ASCVD. These studies provide new insights into Lp(a) pro-inflammatory properties and are especially relevant in view of therapies targeting APO(a) to decrease cardiovascular risk.

Identifiants

DOI: 10.1016/j.atherosclerosis.2024.117474 PMID: 38428286
pubmed: 38428286
pii: S0021-9150(24)00034-0
doi: 10.1016/j.atherosclerosis.2024.117474
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

117474

Informations de copyright

Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Auteurs

Anouk G Groenen (AG)

Department of Pediatrics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.

Anastasiya Matveyenko (A)

Columbia University Irving Medical Center, College of Physicians and Surgeons, Department of Medicine, Division of Preventive Medicine and Nutrition, New York, NY, USA.

Nelsa Matienzo (N)

Columbia University Irving Medical Center, College of Physicians and Surgeons, Department of Medicine, Division of Preventive Medicine and Nutrition, New York, NY, USA.

Benedek Halmos (B)

Department of Pediatrics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.

Hanrui Zhang (H)

Columbia University Irving Medical Center, Division of Cardiology, New York, NY, USA.

Marit Westerterp (M)

Department of Pediatrics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands. Electronic address: m.westerterp@umcg.nl.

Gissette Reyes-Soffer (G)

Columbia University Irving Medical Center, College of Physicians and Surgeons, Department of Medicine, Division of Preventive Medicine and Nutrition, New York, NY, USA. Electronic address: gr2104@cumc.columbia.edu.

Classifications MeSH