The role of serum biomarkers and oxidative stress in Ischemic Heart Disease

Riley, C

Abstract

Ischemic heart disease also referred to as coronary artery disease (CAD) is a leading cause of death worldwide. The primary pathological mechanism underlying CAD is atherosclerosis, an inflammatory process associated with an accumulation of lipids and metabolic alterations within the coronary arteries, and increased cytokine levels and oxidative stress (OS) in the myocardium. Previous studies focused on the use of small animals to model the pathophysiology of CAD. However, CAD is a multifactorial disease and the extent to which inflammatory markers and oxidative stress are elevated in CAD patients is not fully understood. This limits the reliability of those previous studies.
To address this, this preliminary study sought to measure plasma levels of interleukin-1β (IL-1β; a pro-inflammatory cytokine), and oxidised-low density lipoprotein (Ox-LDL, a marker of OS) in a CAD patient cohort and correlate to indices of cardiac function. Furthermore, OS tolerance in isolated cardiac myocytes was examined to elucidate the role of reactive oxygen species (ROS), thus OS mechanisms in CAD pathology.
The study was conducted in accordance with IRAS ethical approval (ID: 247341). Preoperative plasma IL-1β and Ox-LDL levels were quantified using enzyme-linked immunosorbent assays. Indices of cardiac function were acquired from patient echocardiology records. In parallel right atrial appendage tissue was obtained for isolation of cardiac myocytes. Subsequently, Cytation fluorescence imaging was used to measure baseline OS and in response to hydrogen peroxide (H2O2) challenge.
Average serum IL-1β and Ox-LDL concentrations were 1.46 ± 0.26 pg/ml (n = 31) and 32.76 ± 6.15 ng/ml (n = 37) respectively. Peak E wave velocity negatively correlated with plasma IL-1β concentration (n = 13, R2 = 0.4506, p = 0.0120). Tricuspid annular plane systolic excursion (TAPSE) positively correlated with plasma Ox-LDL levels (n = 15, R2 = 0.3067, p = 0.0322). Other indices of systolic function, ejection fraction, did not correlate with either IL-1β or Ox-LDL. Preliminary Cytation fluorescence imaging analysis revealed a significant increase in fluorescence at both 100 µM (27 ± 9 %, n = 13, p <0.05) and 200 µM (62 ± 9 %, n = 8, p <0.001), hydrogen peroxide concentrations. This was associated with a significant difference between patients (n = 3, p <0.001).
These data show that IL-1β may be a valuable biomarker in assessing the severity and progression of myocardial dysfunction in CAD. Oxidative stress increased in response to H2O2 which validated our method. Importantly this OS was heterogeneous across patients, which may be a result of diminished antioxidant capacity in cardiac myocytes.
While these findings indicate that inflammation and OS play a crucial role in CAD pathology, further research is required to increase the study power and elucidate the underlying mechanisms.

Citation

Riley, C. The role of serum biomarkers and oxidative stress in Ischemic Heart Disease. (Dissertation). University of Salford

• Thesis Type: Dissertation
• Deposit Date: Apr 12, 2023
• Publicly Available Date: Apr 12, 2023
• Award Date: Oct 25, 2022