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Circulating soluble IL-6 receptor associates with plaque inflammation but not with atherosclerosis severity and

Andreas Edsfeldt1, Isabel Gonçalves2, Isa Vigren3

  • 1Department of Clinical Sciences Malmö, Lund University, Sweden; Department of Cardiology, Skåne University Hospital, Sweden; Wallenberg Center for Molecular Medicine, Lund University, Sweden.

Vascular Pharmacology
|August 27, 2023
PubMed

Insights

High levels of Interleukin-6 (IL-6) are linked to increased cardiovascular disease (CVD) risk and atherosclerosis. Soluble IL-6 receptor (sIL-6R) is not a reliable CVD risk marker but reflects plaque inflammation.

Area of Science:

  • Biochemistry
  • Immunology
  • Cardiovascular Medicine

Background:

  • Residual cardiovascular disease (CVD) risk is linked to persistent vascular inflammation.
  • Interleukin-6 (IL-6) is a key mediator of inflammation and a potential therapeutic target.
  • IL-6 exerts its effects through direct receptor binding or via soluble IL-6 receptors (sIL-6R).

Purpose of the Study:

  • To investigate the association between IL-6 and sIL-6R pathways and the risk of cardiovascular disease (CVD).
  • To evaluate the relationship between IL-6/sIL-6R and atherosclerosis, arterial stiffness, and endothelial function.
  • To determine the role of sIL-6R in plaque inflammation.

Main Methods:

  • Analysis of IL-6 and sIL-6R in plasma samples from three large prospective cohorts (MDC, SUMMIT VIP, CPIP) using proximity extension assay.
  • Longitudinal follow-up for incident cardiovascular events (myocardial infarction) and assessment of clinical outcomes.
  • Immunohistochemistry and biochemical analysis of atherosclerotic plaques.

Main Results:

  • Elevated plasma IL-6 levels were significantly associated with an increased risk of myocardial infarction (HR 2.60 [2.08-3.25]).
  • High IL-6 correlated with increased atherosclerosis, arterial stiffness, and impaired endothelial function.
  • Soluble IL-6 receptor (sIL-6R) showed no independent association with CVD risk or vascular function but was linked to plaque inflammation.

Conclusions:

  • Plasma IL-6 is a significant risk marker for cardiovascular events and associated vascular pathologies.
  • Soluble IL-6 receptor (sIL-6R) is not a reliable indicator of overall CVD risk.
  • The association of sIL-6R with plaque inflammation suggests a complex role for IL-6 signaling in atherosclerosis.
Abstract

Keywords:
AtherosclerosisAtherosclerotic plaqueIL-6Myocardial infarctionSoluble IL-6 receptor

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