Abstract
Immune checkpoint inhibitors (ICI) have revolutionized oncological care, but cardiovascular immune related adverse events are feared. There is growing evidence suggesting that ICI accelerate atherosclerosis or even lead to increased risk for acute coronary syndromes. The current proposal studies the effects of ICI on the cardiovascular system, hypothesizing that ICI induce endothelial inflammation and dysfunction. VCAM-1 is expected to be key in these processes and could function as a potential target in future project proposals. Mice (C57/Bl6 and ApoE-/-) will be treated with ICI for one week and undergo in vivo functional cardiovascular assessment with echocardiography and pulse wave velocity. Upon sacrifice, ex vivo endothelial function will be studied and inflammatory markers will be analyzed.
The purpose of this proposal is to demonstrate early endothelial inflammation and VCAM-1 upregulation after ICI treatment. This hypothesis was incorporated in previous grant proposals (FWO Junior Project, Stand up against Cancer, Foundation against Cancer) and was positively reviewed and considered relevant and novel, but preliminary data were absent. With this BOF Small Research Grant, preliminary data will be obtained to apply for further funding and start this new line of research within GENCOR.
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