Neutrophils: emerging role in the immunopathology of atherosclerosis

This thesis demonstrates the crucial role of neutrophils in the onset and progression of atherosclerosis. Although neutrophils represent just a small population within the plaque when compared to macrophages, they have to be considered as important promoters of lesion formation. The work presented here demonstrates that increased neutrophil production correlates with the pro-inflammatory phenotype and enlargement of lesions. Neutrophil death is central to resolution. However, the lifespan of neutrophils during atherosclerosis is delayed, which we identified is mediated by the chemokine PF4 released by activated platelets. On this note, strategies aiming at the promotion of neutrophil apoptosis could be of high interest. Finally we establish a mouse model that allows studying the impact of neutrophils on vulnerable plaque progression. Thus, the comparative study of the vulnerable plaque mouse models can set the basis to study neutrophil targeted treatment, such as inhibition of neutrophil production, recruitment, and degranulation. Hence, findings from this thesis may open new strategies and therapeutic approaches for the future.