Finlands Akademi  
Sökande / Kontakt person Kaikkonen-Määttä, Minna
Organisation Östra Finlands universitet
Projektets titel Macrophage phenotypic polarization during atherogenesis in disease-associated tissues
Beslutnr 333021
Beslutsdatum 27.05.2020
Finansierings period 01.09.2020 - 31.08.2024
Finansiering 494 448
Beskrivning av projektet
Atherosclerosis is a chronic inflammatory process, where macrophage accumulation is linked to higher risk of plaque rupture. Nonetheless, our understanding of how atherogenesis affects macrophage plasticity and heterogeneity within disease-relevant tissues remains in its infancy. Here we aim to investigate macrophage specific gene expression during disease progression in aorta, adipose tissue, liver and blood in mice and humans. Single cell sequencing and spatial transcriptomics are used to characterize the effect of cholesterol, insulin resistance and vulnerable plaque environment on macrophages. The data is integrated to model gene regulatory networks, differentiation trajectories, metabolic switching and ligand-receptor interactions to identify key drivers of polarization. Finally the identified key drivers are validated and their biomarker potential is evaluated to provide mechanistic understanding of macrophage polarization and uncover indicators of disease state.