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Macrophages as Key Regulators of Repair in Injured Myocardial and Skeletal Muscle

Description: Cardiovascular diseases, including myocardial infarction and peripheral artery disease, result in ischemia, tissue injury, and severe functional impairment. Efficient treatments to limit tissue damage and enhance healing following an ischemic event is lacking. Building on our previous findings of regenerative functions of innate immune cells at sites of ischemic injury, the current project aims to identify targets for future immunotherapies by delineating the full potential and underlying regulation of macrophages in the inherent repair program. This will be achieved by my established experimental framework combining world-unique preclinical models with functional non-invasive assessments of blood flow and echocardiography, as well as high-resolution molecular profiling using single-cell sequencing, spatial omics and intravital microscopy. I propose to apply these technologies on three distinct cardiovascular disease models—hind limb ischemia, myocardial infarction, and high-pressure overload—in both Spiny mice, known for their remarkable regenerative capacity, and transgenic mice. Using this approach, we will identify novel macrophage effector functions important for limiting and reversing ischemic disease. Lastly, proof-of-concept experiments will be performed where these distinct macrophage effector functions are therapeutically enhanced will be performed in a clinically relevant setting of underlying metabolic challenge.
Amount: SEK 6,150,000
Funding type: research
Funder scheme: Project grant
Start date: 2026-01-01
End date: 2029-12-31
Investigator: Mia Phillipson
Institution: Uppsala University
Funded outputs count: 0
Funder award ID: 2025-02887
OpenAlex ID: G3267638717
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