Sex Bias in Cytokines Transported by High‐Density Lipoproteins in Patients with Coronary Artery Disease

Abstract

Inflammation plays an important role in the induction of Coronary Artery Disease (CAD) and the progression to deadly coronary syndromes. Cytokines are key mediators of inflammation, both in pro‐ and anti‐inflammatory capacities. We have recently discovered that cytokines are transported by high‐density lipoproteins (HDL), suggesting a novel mechanism contributing to the anti‐inflammatory effects of HDL. We examined the HDL‐associated cytokine profiles of male and female patients with CAD to better understand the differences in coronary disease presentation and therapeutic response between men and women.MethodsPatients with confirmed CAD, defined by history of myocardial infarction, coronary artery bypass surgery, or angiography, with controlled serum lipid levels were included in the study. Native HDL species were isolated from plasma samples by selected‐affinity immunosorption. Plasma and isolated HDL samples were assayed for cytokine content by a multiplex array detecting the quantity of 35 cytokines.ResultsThe majority of cytokines assayed were measurable in HDL samples. The distribution of HDL‐associated cytokines varied significantly between males and females. Female HDL samples indicate a much greater degree of remodeling of cytokine cargo than males. Cluster analysis of cytokine expression patterns suggests a difference in inflammatory pathway activation and response in females with CAD.ConclusionsThe cytokines transported by HDL in CAD patients differs greatly between men and women. The pattern of HDL‐associated cytokines provide new insights into the inflammatory processes contributing to CAD in a sex‐dependent manner. The amount of cytokine‐HDL remodeling is exhibited to a greater degree in females; the physiological relevance of this phenomenon is unknown. We aim to elucidate the mechanism of HDL transport of these cytokines and the clinical implications of sex differences in inflammatory response in CAD in future studies.Support or Funding InformationThis work is supported by the Read Family Foundation and the Campini Foundation.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.