MicroRNA-21 Deficiency Alters the Survival of Ly-6C ^lo Monocytes in ApoE ^−/− Mice and Reduces Early-Stage Atherosclerosis—Brief Report

Abstract

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 lo nonclassical monocytes in comparison to Ly-6C hi monocytes. The absence of miR-21 significantly altered the survival and number of circulating Ly-6C lo 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 lo nonclassical monocytes homeostasis and contribute to limit early-stage atherosclerosis.

miR‑21/PTEN pathway mediates the cardioprotection of geniposide against oxidized low‑density�lipoprotein‑induced endothelial injury via suppressing oxidative stress and inflammatory response

“…Previous studies have confirmed that miR-21 in endothelial cells is significantly increased in atherosclerotic plaques and that it causes pharmacological effects by directly targeting the PTEN tumor suppressor gene, indicating a pivotal effect of the miR-21/PTEN pathway in atherosclerosis (24,25). A number of reports have indicated that the miR-21/PTEN pathway regulates important functions of Ecs, apoptosis and inflammatory responses during atherosclerosis (26,27). However, the exact actions of the miR-21/PTEN pathway in the progression of atherosclerosis and in the cardioprotection of geniposide remain unknown.…”

MicroRNAs: Fine Tuners of Monocyte Heterogeneity

“…Recently, the group of Stéphane Potteaux identified an miRNA critical for generating Ly6C low monocytes. The authors observed increased expression of miR-21 in non-classical Ly6C low monocytes of atherosclerotic ApoE −/− mice, which mediated their higher number and lifespan in this model (59). The frequency of Ly6C low monocytes in blood, bone marrow and spleen was markedly reduced in ApoE −/− miR-21–deficient mice.…”

Genistein alleviates chronic vascular inflammatory response via the miR‑21/NF‑κB p65 axis in lipopolysaccharide‑treated mice

“…In vivo, miR-21 knockout alters the homeostasis of Ly-6C lo cells and reduces the formation of early atherosclerotic lesions in apolipoprotein E knockout mice (26), while in low-density lipoprotein receptor knockout mice, miR-21 knockout leads to inflammatory cell accumulation, defects in efferocytosis and accelerated development of advanced atherosclerosis (25). Furthermore, miR-21 knockout exacerbates angiotensin II-induced thoracic aortic aneurysm and dissection formation in mice, which may be associated with the TGF-β/SMAD3 signaling pathway (27).…”