Abstract
The present study aims to investigate the mechanism of miR-15a-5p in the atherosclerotic (AS) inflammatory response and arterial injury improvement in diabetic rats by regulating fatty acid synthase (FASN). Initially, bioinformatics tools were applied to evaluate miRNAs and genes correlating with AS, and the target relation between miRNAs and FASN was measured using the Dual-Luciferase Reporter Assay. Subsequently the diabetic AS rat model was established and the surviving rats were divided into: negative control (NC), miR-15a-5p mimic, miR-15a-5p inhibitor, sh-FASN and miR-15a-5p + sh-FASN groups. Then a series of experiments were performed to examine the degree of AS in each group. The results revealed that compared with the NC group, the expressions of C-reactive protein (CRP), interleukin 6 (IL-6), intercellular cell adhesion molecule-1 (ICAM1) in rat arterial tissue, as well as the levels of low-density lipoprotein cholesterol (LDL-C), blood glucose (BG), triglycerides (TG), total cholesterol (TC) and Homocysteine (Hcy) in rat serum, were increased after inhibiting miR-15a-5p, while the level of high-density lipoprotein cholesterol (HDL-C) was decreased and the fat storage area was enlarged after this treatment (P<0.05). In the miR-15a-5p mimic and sh-FASN groups, serum HDL-C levels were increased and the fat storage areas in arteries were reduced. The levels of CRP, IL-6, ICAM1 in rat arterial tissue, along with the levels of LDL-C, BG, TG, TC and Hcy in rat serum, were decreased (P<0.05). Hematoxylin and Eosin (HE) staining and transmission electron microscopy (TEM) results showed AS lesions to be apparent in the arteries of rats in both the NC and miR-15a-5p inhibitor groups, but that in miR-15a-5p and sh-FASN group were improved, the miR-15a-5p mimic + sh-FASN group showed the most obvious improvement. Taken together, miR-15a-5p alleviates the inflammation response and arterial injury in diabetic AS rats by targeting FASN.
Highlights
Diabetes is a common disease that can lead to a higher risk of cardiovascular disease (CVD) and certain severe polyvascular complications, including arteriosclerosis and peripheral arterial disease [1,2]
The results revealed that compared with the negative control (NC) group, the expressions of C-reactive protein (CRP), interleukin 6 (IL-6), intercellular cell adhesion molecule-1 (ICAM1) in rat arterial tissue, as well as the levels of low-density lipoprotein cholesterol (LDL-C), blood glucose (BG), triglycerides (TG), total cholesterol (TC) and Homocysteine (Hcy) in rat serum, were increased after inhibiting miR-15a-5p, while the level of high-density lipoprotein cholesterol (HDL-C) was decreased and the fat storage area was enlarged after this treatment (P
The results of this study demonstrated that miR-15a-5p can improve AS in mice from two aspects that it can reduces the inflammatory response of endothelial cells and accelerates lipid metabolism by targeting fatty acid synthase (FASN)
Summary
Diabetes is a common disease that can lead to a higher risk of cardiovascular disease (CVD) and certain severe polyvascular complications, including arteriosclerosis and peripheral arterial disease [1,2]. Atherosclerosis (AS), a specific form of arteriosclerosis, is a chronic disease of the arterial wall that represents a main cause for the loss of productivity and increased rates of deaths worldwide [3,4]. AS risk results from several factors, including being of the male gender, having hypertension and family history of illness [5]. The structural and functional integrity of the endothelium is crucial in maintaining cardiovascular homeostasis and preventing AS [7]. Dysfunctions of the endothelium and arterial vasculature are primary culprits for atherosclerotic CVD and the progression of AS [8,9]
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