The Role of lnterleukin-8 In lschemic Heart Disease and Oxidative Stress

Ioannidi, Anna

Abstract

Ischemic heart disease also known as coronary heart disease remains a primary cause of mortality and morbidity worldwide (Nowbar et al., 2019). Several mechanisms are involved in the development of the condition, such as chronic inflammation and the imbalance between the formation of reactive oxygen species (ROS) and antioxidant defenses also called oxidative stress (Beteridge 2000). Chronic inflammation seems to be playing a key role in the progression of the disease as well as the long-term prognosis. Since the establishment of the link between inflammation and the prediction of cardiovascular events, several pro-inflammatory cytokines have been examined as potential biomarkers and therapeutic targets (Vilela & Fontes-Carvalho, 2021). To further elucidate potential biomarkers, this study measured the levels of pro-inflammatory cytokine IL-8 in 52 CAD patients’ serum with the goal to investigate the possible correlation between those levels to cardiac function. The average concentration of IL-8 was 5.77± 5.81 pg/mL (n=38), while 14 patients’ IL-8 levels were undetectable. Trends were observed between the correlation of IL-8 and Ejection fraction (EF) (p= 0.0684, r2= -0.3163, n= 34) and the correlation between IL-8 and the Body Mass Index (BMI) (p=0.0784, r2=0.2358. n=14). While other parameters did not correlate with IL-8. For example, no correlation was observed between levels of IL-8 , Left ventricular outflow tract (LVOT) (p=0.4073, r2=0.04330, n=18) or between Tricuspid annular plane systolic excursion (TAPSE) (n=21, r2 = 0.009047, p= 0.6817). No correlations were observed between the levels of IL-8 and the Age and Heart Rate (HR) (n=34, r2 = 0.02481, p=0.3736) and (n=18, r2 = 0.0970, p=0.2091) respectively. In addition to that, no significant difference between the levels of IL-8 was observed between the male (n=16) and female (n=6) patients of the study cohort (p= 0.2851). Finally, to further understand the involvement of IL-8 in IHD, different concentrations of the cytokine along with hydrogen peroxide, an established ROS inducer that was employed as a positive control, were introduced to rat cardiomyocytes to investigate the possible dose-dependent effects in oxidative stress production. Data demonstrated that the two different concentrations of IL-8 (6 pg/mL and 50 ng/mL) alone did not cause a significant increase in oxidative stress levels (n= 8, p>0.05). However, an increase in OS was observed when 50 ng/mL were co-introduced to H9C2 cells along with 100μΜ of H2O2 (n= 8, p<0.01) compared to the H9C2 cells that were only exposed to the 100μΜ of H2O2. In addition to that both concentrations of 6pg/mL, 50 ng/mL IL-8 caused a significant increase in OS (n= 8, p<0.05). These findings suggest that IL-8 could potentially be an important biomarker of ischemic heart disease and its manifestations in cardiac dysfunctions. While its ability to increase levels of OS in an ischemic model supports IL-8 involvement in the interplay of inflammation and oxidative stress in CAD. Further research is important to increase the study’s power and validate these results.

Citation

Ioannidi, A. (2023). The Role of lnterleukin-8 In lschemic Heart Disease and Oxidative Stress. (Thesis). University of Salford

• Thesis Type: Thesis
• Deposit Date: Nov 13, 2023
• Publicly Available Date: Nov 28, 2023
• Award Date: Oct 27, 2023