Prins, F.M. (Femke) (2019) Inflammation in coronary artery disease: the role of interleukin-6 and the human gut microbiome. thesis, Medicine.
Full text available on request.Abstract
Introduction: Inflammation plays an important role in the development of atherosclerosis, which is a component in the pathophysiology of coronary artery disease (CAD). The onset of inflammation is thought to be affected by many factors, including cytokines such as interleukin 6 (IL-6) and the gut microbiome. However, the precise roles of these inflammatory factors in CAD remain to be elucidated. Therefore, this study investigated both the associations of IL-6 in the development and during an event of CAD as well as the associations of the gut microbiome and development of CAD. Material & Methods: As a proxy for IL-6 levels, genetic variations caused by single nucleotide polymorphism (SNPs) were used. Five SNPs known to affect IL-6 levels were selected and used for logistic and linear regression analyses on cardiovascular (health) outcomes, longevity, hemodynamic traits and blood count from participants of the UKBiobank. Statistical significance adjusted for multiple testing was considered as p < 2.00·10-4. For the analysis of IL-6 in an acute CAD event, 24 patients were included. Peripheral blood mononuclear cells and plasma was collected at three time points: baseline (T1), 24 hours after percutaneous intervention (T2) and at 6-8 weeks (T3). For the microbiome analysis, 508 SNPs known to affect the gut microbiome were tested for associations with cardiovascular (health) outcomes and linear traits. Statistical significance was considered as p < 3.00·10-3. Results: Increased IL-6 levels were associated with reduced risk of cardiovascular disease (e.g. atherosclerosis, odds ratio (OR) 0.96, 95% confidence interval (CI) 0.95-1.06)), increased cardiovascular health (OR 1.05, 95% CI 1.03-0.97) and increased longevity (β=.028; SE .006). Furthermore, IL-6 levels were significantly elevated 24h after ST-elevated myocardial infarction compared to baseline (p<0.001). Bacteria of the gut microbiome were also associated with CAD outcomes, a total of 35 microbiome SNPs showed significant associations. Discussion: Both IL-6 and bacteria of the gut microbiome show associations with CAD. The exact mechanisms of these interactions should be further explored. However, this study provides starting points for future studies focusing on unraveling the pathways of IL-6 and the gut microbiome in CAD and investigating potential therapeutic targets.
| Item Type: | Thesis (Thesis) |
|---|---|
| Supervisor name: | Daily supervisor: and Groot, H.E.MD and Faculty supervisor: and Harst, Prof. dr. P. van der and University Medical Centre Groningen and Department of Cardiology |
| Faculty: | Medical Sciences |
| Date Deposited: | 25 Jun 2020 10:49 |
| Last Modified: | 25 Jun 2020 10:49 |
| URI: | https://umcg.studenttheses.ub.rug.nl/id/eprint/980 |
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