Dissertation

Stress-induced modulation of the innate immune system in cardiovascular disease

Promotor: Prof.dr. J. Kuiper

Author: H.M. Lagraauw
Date: 22 October 2015
Links: Thesis in Leiden Repository

Atherosclerosis is a chronic inflammatory disease in which lipids and cells of the immune system accumulate in the vessel wall. Clinical complications, such as a myocardial infarction or stroke may occur when advanced atherosclerotic lesions become unstable and rupture. In this thesis, the influence of the psychological stress response and stress-related neuropeptides on vascular inflammation and atherosclerotic lesion development has been investigated. We demonstrated that acute stress results in activation of a potent type of immune cell in the vessel wall, the mast cell, leading to increased inflammation and atherosclerotic plaque destabilization. Furthermore, we have shown that (peri)vascular mast cell activation leads to neutrophil recruitment, thus aggravating the local inflammatory response. In addition, we demonstrated increased expression of neuropeptide Y in advanced atherosclerotic lesions and that overexpression of this peptide results in increased lesion development. These insights emphasize a contributing role for psychological stress to atherosclerotic lesion development and as a risk factor for acute cardiovascular syndromes and opens up new avenues for possible future anti-inflammatory therapies to reduce the risk of cardiovascular disease.