PhD Defence Renée J.H.A. Tillie

Keywords: Slagaderverkalking, microvaatjes, macrofagen, fibroblasten
 

"Plaque stabilizing and destabilizing effects in atherosclerosis: The role of microvessels, macrophage metabolism, and fibroblasts"

Cardiovascular disease is a major global health concern, leading to significant morbidity and mortality. Atherosclerosis, a chronic inflammatory disease, is a key driver of many cardiovascular diseases. Atherosclerosis causes the buildup of fatty deposits, also called plaques, in arteries. Destabilization and subsequent rupture of plaques can trigger serious events such as heart attack and stroke.

This thesis explored potential regulators of atherosclerotic plaque stability, focusing on microvessels, macrophage metabolism, and fibroblasts. Firstly, the effect of modification of the PDGF-B protein on atherosclerotic microvessel leakage and plaque stability was studied. Although atherosclerotic microvessels were unaffected, the modification showed dual effects as it enhanced plaque stability, while also stimulating an inflammatory response in the blood. Additionally, this thesis showed that inhibition of a glycolytic enzyme in macrophages did not affect plaque stability, but led to fatty liver disease instead. Lastly, the role of fibroblasts was explored, revealing their diversity, cell-specific markers, and potential function in atherosclerosis.

Hereby, this thesis identified new leverage points for future treatment development for atherosclerosis and fatty liver disease, which require further investigation.

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