Neutrophils fatten atherosclerotic lesions

• Applicant: Professor Dr. Oliver Söhnlein, since 3/2021
• Subject Area: Anatomy and Physiology ; Cell Biology
• Term: from 2017 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 392310670

Atherosclerosis is a chronic inflammatory disease resulting from a dysbalanced lipid metabolism that leads to cardiovascular complications, which accounted for 31% of global mortality in 2012. So far, lipid lowering therapies are the most promising therapeutic approach. Atherosclerosis is characterized by the accumulation of leukocytes into the arterial wall and the engulfment of LDL particles by macrophages, leading to foam cell formation and therefore plaque engrossment. The development of the plaque at the onset of the disease is dependent on the number of circulating neutrophils, which have been shown to accumulate lipids in circulation at postprandial state. This lipid accumulation may modify the phenotype and functional behaviour of the neutrophils. Despite the poor detection of neutrophils in the plaques, neutrophil granule proteins and NETs have been largely spotted in the lesions. We therefore hypothesize that neutrophils undergo apoptosis shortly after their recruitment into the plaque releasing their content, which may include engulfed lipids, boosting foam cell formation and atherosclerosis worsening. Hence, we aim at studying three key aspects in this project: 1) Neutrophil lipid accumulation and phenotype, 2) Inflammatory function of lipid-laden neutrophils and 3) Contribution of neutrophil lipid accumulation to atherosclerosis. The outcome of this project will shed light not only on the mechanistic understanding of atherosclerosis but also on the discovery of new therapeutic targets.

• DFG Programme: Research Grants
• Ehemalige Antragstellerin: Almudena Ortega-Gomez, Ph.D., until 2/2021