The role of the soluble interleukin 6 receptor in the cardiovascular disease continuum.

Groot, H.E. (Hilde) (2014) The role of the soluble interleukin 6 receptor in the cardiovascular disease continuum. thesis, Medicine.

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Abstract

Background: Cardiovascular disease is a major cause of death in the western world and is projected to remain the single leading cause of death. Currently, numerous studies are ongoing on the role of biomarkers and their targetable mechanisms in cardiovascular diseases. The aim of this study was to investigate the role of soluble interleukin 6 receptor (sIL-6R) in the cardiovascular disease continuum. Methods: To investigate the role of sIL-6R, we developed a sIL-6R enzyme-linked immunosorbent assay (ELISA) and analyzed serum samples of two different patient groups (ST-elevated myocardial infarction (STEMI), ischemic heart failure (IHF)) and healthy controls. We investigated the association of IL-6R gene variants with sIL-6R levels, we investigated the sIL-6R levels of the two patient groups and the healthy controls, and we investigated the association between myocardial reperfusion and sIL-6R levels. Results: We developed and validated a cost-effective sIL-6R ELISA. sIL-6R levels were measured in 70 STEMI patients, 30 IHF patients and 34 offspring of IHF patients, and 23 healthy controls and 31 offspring of healthy subjects. Variance in sIL-6R levels could be partly genetically explained (30%). A genetic variant (rs7529229) was significantly associated with sIL-6R levels. STEMI patients tended to have lower sIL-6R levels than healthy controls and IHF patients (80.92 ng/ml vs. 94.90 ng/ml and 86.17 ng/ml) and their sIL-6R levels had a transiently fluctuating character in the acute phase of STEMI. Furthermore, differences in sIL-6R levels between baseline and post-PCI had a predictive value for myocardial reperfusion. sIL-6R levels in IHF patients were similar to the sIL-6R levels in healthy controls. Conclusion: In conclusion, we investigated the association of sIL-6R with several of the stages of the cardiovascular disease continuum. We did observe changes in sIL-6R levels after myocardial infarction and a possible association between fluctuation in sIL-6R levels and myocardial reperfusion. Further research is needed to elucidate whether these associations of IL-6 and sIL-6R with STEMI and IHF are causal and should be considered further as a therapeutic target.

Item Type:	Thesis (Thesis)
Supervisor name:	Harst, Dr. P. van der
Faculty:	Medical Sciences
Date Deposited:	25 Jun 2020 10:53
Last Modified:	25 Jun 2020 10:53
URI:	https://umcg.studenttheses.ub.rug.nl/id/eprint/1369

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