# Increased CX3CL1/CX3CR1 Axis Is Related to Atherosclerosis in Subjects with Familial Combined Hyperlipidaemia, Which Is Modulated by Insulin Resistance but Not by Sex

## TL;DR

This study shows that the CX3CL1/CX3CR1 axis is more active in people with familial combined hyperlipidaemia and is linked to insulin resistance, not sex, increasing their risk of atherosclerosis.

## Contribution

The study identifies the role of the CX3CL1/CX3CR1 axis in familial combined hyperlipidaemia and its modulation by insulin resistance.

## Key findings

- FCH subjects showed significantly higher activation of the CX3CL1/CX3CR1 axis compared to controls.
- FCH individuals with insulin resistance had worse inflammation, higher carotid IMT, and more atherosclerotic plaques.
- Sex did not influence the CX3CL1/CX3CR1 axis in FCH patients.

## Abstract

Background: A major factor in the development of atherosclerosis is the presence of a chronic inflammatory state. The CX3CL1/CX3CR1 axis has been implicated in the development of atherosclerosis and cardiovascular disease, but until now, scarce data are available regarding the influence of the CX3CL1/CX3CR1 axis in familial combined hyperlipidaemia (FCH). Since FCH is associated with a high risk of cardiovascular disease, the objective of the present study was to assess the presence of alterations in the CX3CL1/CX3CR1 axis in patients with FCH and to evaluate the influence of insulin resistance (IR) and sex. Methods: A cohort of 47 subjects with FCH and 38 control subjects was included. We measured the lipid profile, glucose, and insulin levels in plasma, circulating blood CX3CL1 levels, and CX3CR1 mRNA expression. Carotid IMT and the presence of atheroma plaques were also evaluated. Results: FCH subjects showed significantly higher activation of the CX3CL1/CX3CR1 axis than controls. In addition, FCH individuals with IR showed the worst profile of inflammation status, higher carotid IMT, and a higher prevalence of atherosclerotic plaque compared to controls and FCH patients without IR. However, sex did not influence the CX3CL1/CX3CR1 axis. Conclusions: FCH patients showed an increased CX3CL1/CX3CR1 axis, which was positively correlated with IR, but not with sex. These data could partially explain the increased risk of cardiovascular events in primary dyslipidemic patients.