Dissertation

Innate immune modulation in atherosclerosis and vascular

Promotores: Prof.dr. J. Kuiper, Prof.dr. P.H.A. Quax

Author: A. Wezel
Date: 11 December 2014
Links: Thesis in Leiden Repository

Atherosclerosis is a chronic inflammatory disease, consisting of the buildup of lipids in the vessel wall. Advanced lesions may become unstable and rupture, leading to major cardiovascular complications such as myocardial infarction or stroke. In this thesis, the role of the innate immune system in atherosclerosis has been investigated. We have shown that inhibition of complement component C5a results in reduced atherosclerotic lesion formation as well as reduced lesion destabilization. Also, we have provided evidence that activation of mast cells surrounding the atherosclerotic lesion results in increased accumulation of the neutrophil, thus aggravating the local inflammatory response. Moreover, we have investigated the effect of microRNA inhibition of atherosclerosis. MicroRNAs are short non-coding RNA strands with the ability to modulate the expression of multiple genes. With a unique Reversed Target Prediction we have identified microRNAs that are predicted to affect multiple atherosclerosis-related genes. We inhibited one of these predicted microRNAs: microRNA-494, and investigated its role in vivo. Interestingly, we observed a striking reduction in atherosclerotic lesion formation, as well as an increase in lesion stability.