The Role of Tumour Necrosis Factor-α in Coronary Artery Disease

Staley, Alicia

Abstract

Coronary artery disease (CAD) is a chronic inflammatory condition associated with high rates
of mortality worldwide. Pro-inflammatory cytokines such as tumour necrosis factor (TNFα)
play a key role in CAD pathogenesis, though the degree to which TNFα is elevated, or alters
cardiac function in CAD remains unclear. CAD is also associated with elevated levels of reactive
oxygen species (ROS) in the heart, though the extent to which this is dependent on cytokines
isn’t known. This preliminary study sought to (1) quantify plasma TNFα levels in a CAD patient
cohort then correlate those levels to measurements of systolic and diastolic cardiac function,
and (2) establish whether clinically relevant concentrations of (TNFα) elevate intracellular
oxidative stress.
The study was conducted in accordance with local and IRAS ethical approval (IRAS ID: 247341).
Blood samples were taken from consenting patients scheduled for revascularisation surgery.
TNFα levels were measured using a high-sensitivity ELISA kit. Measurements of cardiac
function were extracted from patient clinical records. Fluorescent imaging was used to
quantify levels of oxidative stress and cytokine signalling in H9C2 rat myoblasts treated with
supraphysiological and clinically relevant concentrations of TNFα.
Average plasma TNFα levels were 2.27 ± 0.35 pg/ml (n = 66). Preliminary data indicates that
E/A ratio negatively correlates with TNFα concentration (p = 0.0489; r2 = n = 45). TNFα levels
may correlate with LVIDD, though this did not reach significance (p = 0.06; r2 = 0.09; n = 38).
We observed no significant correlations with other indices of systolic and diastolic function
including EF (p = 0.6993; r2 = 0.0031; n = 51) and E/e ratio (p = 0.3297; n = 30). We observed
no significant increase in oxidative stress following treatment with an acute or clinically
relevant concentration of TNFa, which were 50ng/ml and 2pg/ml, respectively.
These preliminary data suggest that plasma TNFα levels may be of limited use as a diagnostic
biomarker in CAD. Furthermore, clinically relevant concentrations of TNFα do not appear to
elevate levels of oxidative stress in our H9C2 rat myoblast model. However, further work
should aim to increase study power, stratify patients according to potential confounding
variables upon complete acquisition of clinical data, and investigate cellular mechanisms that
link TNFα levels with whole heart dysfunction

Citation

Staley, A. (2024). The Role of Tumour Necrosis Factor-α in Coronary Artery Disease. (Thesis). University of Salford

• Thesis Type: Thesis
• Deposit Date: Oct 3, 2024
• Publicly Available Date: Nov 25, 2024
• Award Date: Oct 24, 2024