Dasatinib suppresses atherosclerotic lesions by suppressing cholesterol uptake in a mouse model of hypercholesterolemia

Autor: Masamitsu Takaba, Takayuki Iwaki, Tomohiro Arakawa, Takaaki Ono, Yuichiro Maekawa, Kazuo Umemura
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Journal of Pharmacological Sciences, Vol 149, Iss 3, Pp 158-165 (2022)
Druh dokumentu: article
ISSN: 1347-8613
DOI: 10.1016/j.jphs.2022.04.009
Popis: Although the use of BCR-ABL1 tyrosine kinase inhibitors (TKIs) for chronic myeloid leukemia is known to cause vascular adverse events (VAEs), the frequency of VAEs during dasatinib administration is not high, and the same holds for atherosclerosis-related VAEs. However, its effect on atherosclerosis remains controversial. In this study, our primary objective was to investigate how dasatinib affects atherosclerosis. Ldlr−/−/Apobec1−/− mice, which are highly prone to develop atherosclerosis, were administered dasatinib. After 16 weeks, we evaluated their atherosclerotic lesions. We used bone-marrow-derived macrophages to investigate the uptake of oxidized low-density lipoprotein (LDL) complexed with DiI dye (DiI-oxLDL). RNA sequencing and quantitative reverse transcription polymerase chain reaction (RT-qPCR) were performed to explore the potential effects of dasatinib on cholesterol metabolism. Dasatinib administration significantly reduced atherosclerotic lesions (P
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