MicroRNA-21 Deficiency Alters the Survival of Ly-6C Monocytes in ApoE Mice and Reduces Early-Stage Atherosclerosis-Brief Report.
Fiche publication
Date publication
février 2019
Journal
Arteriosclerosis, thrombosis, and vascular biology
Auteurs
Membres identifiés du Cancéropôle Est :
Dr POTTEAUX Stéphane
Tous les auteurs :
Chipont A, Esposito B, Challier I, Montabord M, Tedgui A, Mallat Z, Loyer X, Potteaux S
Lien Pubmed
Résumé
Objective- To determine the role of microRNA-21 (miR-21) on the homeostasis of monocyte subsets and on atherosclerosis development in ApoE (apolipoprotein E) mice. Approach and Results- In ApoE mice, miR-21 expression was increased in circulating Ly-6C nonclassical monocytes in comparison to Ly-6C monocytes. The absence of miR-21 significantly altered the survival and number of circulating Ly-6C nonclassical monocytes in ApoE mice. In the early stages of atherosclerosis, the absence of miR-21 limited lesion development both in the aortic sinus (by almost 30%) and in the aorta (by almost 50%). This was associated with less monocyte availability in circulation and increased apoptosis of local macrophages in plaques. At later stages of atherosclerosis, lesion size in the aortic root was similar in ApoE and ApoE miR-21 mice, but plaques showed a less stable phenotype (larger necrotic cores) in the latter. The loss of protection in advanced stages was most likely because of excessive inflammatory apoptosis related to an impairment of local efficient efferocytosis. Conclusions- Gene deletion of miR-21 in ApoE mice alters Ly-6C nonclassical monocytes homeostasis and contribute to limit early-stage atherosclerosis.
Mots clés
aorta, atherosclerosis, homeostasis, macrophages, monocytes
Référence
Arterioscler Thromb Vasc Biol. 2019 02;39(2):170-177