The role of interleukin-10 in coronary artery disease

Samphire-Noden, Bethan

Abstract

Coronary artery disease (CAD) is a leading cause of mortality and morbidity worldwide, accounting for 66,000 deaths annually in the UK. Atherosclerosis is the underlying pathophysiological mechanism which drives CAD progression, producing an inflammatory state within coronary arteries reflected by increased cytokine levels. Oxidative stress (OS) arises through imbalance of reactive oxygen species (ROS) and antioxidants and has been indicated as a key player in development and progression of atherosclerosis. We know increased levels of cytokines and OS are associated in cardiac dysfunction in other diseases, but it isn’t clear in CAD.

This study sought to measure serum levels of IL-10 in a CAD patient cohort and correlate to indices of systolic and diastolic function. Alongside elucidating the role of pathological IL-10 levels on OS and cellular viability in challenged and non-challenged cells.
This study was conducted in accordance with IRAS ethical approval (ID: 247341). Patient blood samples were collected pre-operatively and IL-10 levels quantified using enzyme-linked immunosorbent assay. Those levels were then correlated to indices of cardiac dysfunction extracted from patient echocardiological (ECHO) records. Levels of oxidative stress and cellular viability were measured using DCFDA and MTT respectively on a microplate reader, in response to hydrogen peroxide challenge.
Average patient IL-10 concentrations were 4.20 pg/ml  0.01 pg/ml (n = 70). Peak E-wave velocity negatively correlated with plasma IL-10 concentration (n = 53, R2 = 0.08, p = 0.04) however, did not correlate with further indices diastolic dysfunction – EDV. Indices of systolic function (EF, LVOT and PASP) did not correlate with IL-10. A significant increase in fluorescence was measured regarding oxidative stress (p = <0.001 and 0.004) in response to H2O2 treatment in addition to a significant decreased in relation to cellular viability (p = 0.02 and 0.03), which validated our method. Microplate reader data showed IL-10 played no role in oxidative stress nor a cardioprotective role in cells with a high baseline OS. These finds were also reflected in cellular viability, with IL-10 having no effect on cellular viability both in challenged and non-challenged cells.

Overall, these findings show IL-10 plays a lesser role regarding CAD, OS and cellular viability than expected. Limited correlations seen in this preliminary study suggest interleukin-10 to be of little use as a biomarker for assessing dysfunction in CAD in relation to both diastolic and systolic function. Further research is required to increase study power.

Citation

Samphire-Noden, B. (2023). The role of interleukin-10 in coronary artery disease. (Thesis). University of Salford

• Thesis Type: Thesis
• Deposit Date: Dec 4, 2023
• Publicly Available Date: Jan 16, 2024
• Award Date: Dec 8, 2023