Apoptotic cell induction of miR-10b in macrophages contributes to advanced atherosclerosis progression in ApoE-/- mice

Cardiovascular Research
Dongliang WangWenhua Ling

Abstract

We previously found that miR-10b inhibits cholesterol efflux from thioglycollate-elicited mouse peritoneal macrophages through repressing ATP binding cassette transporter (ABCA1). Herein, we deciphered the mechanism underlying macrophage miR-10b expression and the role of miR-10b in atherosclerosis. MiR-10b expression was increased in the arteries with advanced but not early atherosclerotic plaques of ApoE-/- mice. Free cholesterol-induced macrophage apoptotic cells (FC-AM) promoted miR-10b expression in mouse resident peritoneal macrophages (RPM) by up-regulation of Twist1/2 in a Mer receptor tyrosine kinase dependent manner. Surprisingly, antagomiR-10b de-repressed ABCA1 in RPM engulfing FC-AM but not in RPM alone or RPM-derived foam cells; systemic delivery of antagomiR-10b enhanced reverse cholesterol transport from RPM engulfing FC-AM but not from RPM or the foam cells in ApoE-/- mice. Mechanistically, RPM engulfing FC-AM possessed sufficient miR-10b functionally repressing ABCA1 expression, whereas RPM and foam cells had little miR-10b incompetently repressing ABCA1 expression. Notably, antagomiR-10b administration reduced advanced plaque size and also enhanced plaque stability in ApoE-/-mice, which were associated with i...Continue Reading

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Citations

Jun 5, 2019·Cardiovascular Research·Themistoklis KatsimichasDimitris Tousoulis
Aug 8, 2019·Cardiovascular Research·Francesca FasoloJason L Johnson
Feb 13, 2020·The Journal of Nutrition·Jiakun ZhengDongliang Wang
Sep 5, 2019·Journal of the American Heart Association·Liping WuJiumei Cao
Mar 17, 2020·Frontiers in Genetics·Michelle M J MensMohsen Ghanbari
Mar 21, 2021·Clinica Chimica Acta; International Journal of Clinical Chemistry·Wujun ChenDongming Xing

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