The roles and mechanisms of miR-26 derived from exosomes of adipose-derived stem cells in the formation of carotid atherosclerotic plaque

Abstract

Background: This study explored the serum concentrations of miR-26 in patients with carotid atherosclerosis (CAS) and defined the roles and mechanisms of miR-26 derived from the exosomes of adipose-derived stem cells (ADSC-exos). Methods: The carotid artery width was diagnosed by ultrasound examination in patients with different degrees of CAS. The serum levels of total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) in patients were detected by biochemistry. The serum levels of miR-26 were determined by quantitative polymerase chain reaction (qPCR). A model of CAS in ApoE −/− mice fed with a rich-fat diet was established to analyze the regulatory effects of serum miR-26 on blood lipids in mice. Adipose mesenchymal stem cell lines transfected with miR-26 were established. The regulatory relationship between the expression levels of inflammatory factors, including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and IL-1β, and the expression levels of miR-26 in the supernatant of each group of cells was determined by qPCR. The ADSC-exos were extracted from ADSCs and injected into model mice through the tail vein. The therapeutic effect of ADSCs expressing miR-26 on model mice was evaluated by detecting the levels of inflammatory factors and blood lipids in the serum of the mice. Results: The degree of atherosclerosis (AS) was positively associated with the intima-media thickness (IMT) of the carotid artery. The serum levels of miR-26 in patients were inversely correlated with the levels of blood lipids (TC, TG, and LDL-C), and positively correlated with HDL-C levels. Similarly, in the CAS mouse model, the serum levels of miR-26 were inversely correlated with the levels of blood lipids (TC, TG, and LDL-C), and positively correlated with HDL-C level. In ADSCs transfected with miR-26, the miR-26 expression in the cell supernatant was negatively regulated by the expression of inflammatory factors, TNF-α, IL-6, and IL-1β, in the cell supernatant. ADSC-exos expressing miR-26 has positive effects on correcting blood lipids and inflammatory factors in the mouse model of CAS.Conclusions: miR-26 has an active role in CAS and may be a novel target for the treatment of CAS in the future.

The translational potential of miR-26 in atherosclerosis and development of agents for its target genes ACC1/2, COL1A1, CPT1A, FBP1, DGAT2, and SMAD7

“…The administration of ADSCs overexpressing miR-26 (IV, 1 × 10 10 /mouse) for two weeks in a CAS model (apoE−/− mice fed a rich-fat diet (21% fat and 0.2% cholesterol) for 12 weeks) reduced carotid intima–media thickness (IMT), TC, TG, and LDL-C by 34.3%, 47.7%, 35.7%, and 22.9%, respectively [ 36 ]. Proprotein convertase subtilisin/kexin type 9 (PCSK9) knockout in apoE−/− mice fed a regular diet (6% fat and 0% cholesterol) for 6 months did not change IMT or TC levels.…”

“…The diagnostic value of miR-26 in atherosclerosis has been investigated in clinical trials and preclinical models [30][31][32][33][34][35]. The serum miR-26 level was negatively associated with serum total cholesterol (TC), triglycerides (TG), and LDL-C and positively associated with HDL-C in patients with carotid atherosclerosis (CAS) and in apoE−/− mice [36]. The miR-26 level in exosomes produced by adipose-derived stem cells (ADSC-exos) was negatively associated with TNF-α, IL-6, and IL-1β, suggesting that the ADSC-exo miR-26 level is a potential biomarker for the diagnosis of lipids and inflammatory factors (Table 1) [36].…”