Characterisation of inflammatory mediators in ischaemic heart disease

Borun, A

Abstract

Coronary artery disease (CAD) is one of the most common causes of death in general population. In the UK it accounts for 64000 deaths annually and there are currently 2.3 million people living with CAD. Persistent inflammation of myocardium is believed to be the major driver of heart pathology. As such, inflammatory mediators such as cytokines have emerged as potential biomarkers for local and systemic inflammation. Therefore, this study aimed to determine if pre-operative cytokine levels are associated with adverse cardiac function in CAD patients. We also sought to optimise a protocol for the isolation of viable cardiac myocytes from human atrial tissue.
All experiments were conducted in accordance with IRAS ethical approval (REC reference: 18/LO/2219). Firstly, protocol for the isolation of cardiomyocytes from the atria of coronary artery bypass graft (CABG) surgery patients was adapted to obtain cells of optimal quality. In parallel, pre-operative levels of interleukin-8 (IL-8), interleukin-1 (IL-1), interleukin-6 (IL-6), interleukin10 (IL-10), tumour necrosis factor alpha (TNFα), and interleukin 12 (IL-12) were measured using a multiplexed cytometric bead array. Reference data from a healthy population was obtained using meta-analysis. Individuals were matched based on age, gender structure, BMI, hypertension status and history of tobacco use. Patient cytokine concentrations were then correlated with clinical data to identify correlations between indices of cardiac function and inflammatory mediators.
Levels of Interleukin-1β and IL-8 fell below the detection limit of the cytometric bead array assay. Detectable cytokine levels in patients were found to be at 3.15±0.44pg/ml for IL-6, 1.72±0.48pg/ml for IL-10, 1.63±0.19pg/ml for TNF-α, 1.72±0.07pg/ml for IL-12. Healthy population cytokine levels were as follow: 3.92±4.33pg/ml for IL-6, 4.40±6.11pg/ml for IL-10, 11.85±8.62pg/ml for TNF-α, and 16.15±12.97pg/ml for IL-12. Analysis showed that only TNF-α and IL-12 levels were significantly different between both groups (p<0.0001).
Correlation of cytokine levels with cardiac function showed significant relationships between ejection fraction and IL-6 (p=0.0005, r=-0.5142) and IL-12 (p=0.0487, r=0.3061), as well as stroke volume and IL-10 (p=0.0070, r=-0.9539), TAPSE and IL-6 (p=0.0214, r=-0.4491), and BMI and IL-10 (p=0.0088, r=-0.4247).
Overall, these findings show that preoperative levels of certain cytokines significantly correlate with certain indices cardiac function in our CAD patient cohort. These results may offer potential targets for therapeutic agents and treatment strategies for improving cardiac function in CAD patients.

Citation

Borun, A. Characterisation of inflammatory mediators in ischaemic heart disease. (Dissertation). University of Salford

• Thesis Type: Dissertation
• Deposit Date: Apr 12, 2023
• Publicly Available Date: Apr 12, 2023
• Award Date: Nov 15, 2022