Neutrophils in atherosclerotic plaque destabilization

• Applicant: Professor Dr. Oliver Söhnlein
• Subject Area: Cardiology, Angiology
• Term: from 2016 to 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 290367521

The primary cause for cardiovascular disease (CVD) is atherosclerosis, a chronic inflammation of the arterial wall resulting in formation of defined plaques. Fibrous cap thinning and necrotic core growth are major inducers of plaque instability and increase the risk of plaque rupture. Existing mechanistic studies on plaque destabilization have mainly been macrophage-centric and translating these into the clinic has largely failed, while the role of neutrophil-instructed inflammation in plaque instability has been neglected. Here, I aim at dissecting the mechanistic contribution of neutrophils to plaque destabilization thus identifying novel therapeutic targets and opening up innovative therapeutic opportunities. Specifically, I will (i) study the overall importance of neutrophils in atherosclerotic plaque destabilization and (ii) identify chemotactic guidance signals attracting neutrophils to advanced atherosclerotic lesions. In parallel, (iii) mechanisms of neutrophil-driven plaque destabilization including neutrophil-derived proteases and neutrophil-borne alarmins will be scrutinized. In the long-run, findings from these studies shall be translated into nanomedicine-based approaches to interfere with neutrophil-instructed plaque weakening. In aim (iv) I will hence test an antibody-based delivery strategy. Thus, the project will make a major contribution to the understanding of mechanisms underlying plaque destabilization and provide novel therapeutic targets.

• DFG Programme: Research Grants