MicroRNA-217 attenuates intima–media complex thickness of ascending aorta measured by ultrasound bio-microscopy and inhibits inflammation and lipid metabolism in atherosclerotic models of ApoE−/− mice

Abstract

BackgroundLittle investigation was done to test the efficiency of microRNA-217 (miR-217) on atherosclerosis in vivo.MethodsApoE−/− mice were used to construct atherosclerotic models and ultrasound bio-microscopy (UBM) was applied to detect the intima–media thickness (IMT) of the ascending aorta. The serum level of miR-217 and correlation with IMT was investigated. After miR-217 mimic administration, the IMT, inflammation, and lipid-associated molecules were assayed.ResultsThe serum level of miR-217 was reduced in ApoE−/− mice and showed a negative correlation with the IMT of the ascending aorta (r2 = 0.5899, p < 0.0001). miR-217 mimic administration attenuated IMT and down-regulated the level of serum triglyceride (TG), total cholesterol (TC), and low-density-lipoprotein cholesterol (LDL-C), while it could up-regulate high-density lipoprotein cholesterol (HDL-C). Inflammation relevant genes, such as F4/80, tumor necrosis factor (TNF)-α, interleukin (IL)-1, IL-6, and monocyte chemoattractant protein (MCP)-1, and lipid metabolism associated gene, such as LDL receptor, class A scavenger receptors (SR-A), scavenger receptor class B type I (SR-BI), CD36, ATP binding cassette subfamily A member 1 (ABCA1), and ATP binding cassette subfamily G member 1 (ABCG1) in the aorta were significantly down-regulated in miR-217 group when compared with atherosclerosis group.ConclusionmiR-217 could down-regulate IMT and modulate the inflammation and lipid metabolism process, which indicates that miR-217 could be a potential treatment option.

MicroRNA‑217 is involved in the progression of atherosclerosis through regulating inflammatory responses by targeting sirtuin 1

“…Additionally, miR-126, miR-150, miR-155 and miR-142-3p have been demonstrated to serve critical roles in the development of atherosclerosis (39)(40)(41)(42). miR-217, which has been widely studied in cancer (15)(16)(17)(18), has been revealed to be upregulated in atherosclerosis (19,20). However, the role and molecular mechanism of miR-217 in atherosclerosis remain largely unknown.…”

“…miRNA (miR)-217 has been studied in various types of cancer including liver cancer, gastric cancer, lung adenocarcinoma and acute myeloid leukemia (15)(16)(17)(18). Previous studies have revealed upregulation of miR-217 in atherosclerosis (19,20). However, whether miR-217 is involved in the development of atherosclerosis through the regulation of macrophages is still unclear.…”

SR-BI as a target of natural products and its significance in cancer

“…Further study showed that miR-125a, but not miR-455 inhibited expression of hepatic SR-BI in the mouse and rat livers as well as the mouse hepatic cell line Hepa 1-6 [176]. It was reported that miR-217 mimic administration in apoE-deficient mice significantly down-regulated SR-BI mRNA levels [177]. The mechanisms of miR-217-mediated regulation of SR-BI are not yet clear.…”

Diagnostic and theranostic microRNAs in the pathogenesis of atherosclerosis

“…However, it has also been reported that miR‐214 suppressed the activation of Ox‐LDL‐initiated autophagy and increased apoptosis in HUVECs . MiR‐34a and miR‐217 are pro‐atherosclerotic and anti‐angiogenic biomarkers that can induce senescence of endothelial cells by inhibiting the expression of SirT1 . As a functional marker in apoptosis, is recognized as a therapeutic target for atherosclerosis .…”