Browsing by Author "Woller, Katherine Elizabeth Kyllikki"

Stroke attained its status as the third leading cause of death and disability combined in 2019. During that same year, over 62% of all strokes that occurred globally were ischemic, and approximately 10-20% of ischemic strokes have an etiology of carotid atherosclerosis. Atherosclerosis is characterized by atherosclerotic plaques which disturb the vascular lumen and are prone to rupture, potentially resulting in abrupt thrombotic occlusion or thromboembolization into cerebral arteries. Carotid atherosclerosis ultimately manifests itself in two ways: as a stable or an unstable atherosclerotic plaque. Unfortunately, it is difficult to predict the behavior of carotid plaques solely based on radiological assessment, and there is controversy surrounding its utility, particularly in the diagnosis of high-risk asymptomatic plaques. The process of plaque development is intimately linked to the mechanisms of inflammation. Therefore, the investigation of cytokines is warranted to further understand their involvement in the progression of atherosclerosis. Previous studies in the setting of coronary atherosclerosis have found an increase in the level of the pro-inflammatory cytokines, IL-6 and IL-8, and a decrease in the concentration of the anti-inflammatory cytokine IL-10, in patients with unstable angina. Therefore, these three interleukins were measured in this project in a cohort of 500 carotid atherosclerosis patients using AlphaLISA. AlphaLISA is a highly sensitive and streamlined alternative to ELISA, the traditional method for measuring analyte concentrations. The superior sensitivity of AlphaLISA renders it particularly suitable for the measurement of signaling molecules, such as interleukins, as they occur in relatively low concentrations within serum. Remarkably, AlphaLISA requires particularly low sample volumes, only 5 µl of patient serum per well. The primary aim of this Thesis was to explore the potential of these promising circulating cytokines (IL-6, IL-8, IL-10) as clinical biomarkers of carotid plaque vulnerability as well as ascertain other associated plaque-related factors with the highly sensitive method, AlphaLISA. Several meaningful findings were revealed from the analysis of our data which were collected in a large clinical cohort of carotid atherosclerosis patients. We found that circulating concentrations of both IL-6 and IL-10 were increased in patients with symptomatic plaques. Additionally, we discovered that patients with more severe symptom type displayed increased levels of IL-6 and IL-10. We also identified significant positive associations between IL-8 and intramural calcification as well as between IL-10 and intramural hemorrhage. These preliminary analyses demonstrate that the connection between interleukins and atherosclerosis previously established in coronary artery disease remains true in the setting of carotid atherosclerosis as well. In the future, further analyses will be performed and include multivariate statistical models to evaluate the independent value of interleukins for predicting symptoms caused by carotid atherosclerosis.