The Accelerated Progression of Atherosclerosis Correlates with Decreased miR-33a and miR-21 and Increased miR-122 and miR-3064-5p in Circulation and the Liver of ApoE-/- Mice with Streptozocin (STZ)-Induced Type 2 Diabetes

Abstract

Atherosclerosis is a major risk factor for type 2 diabetes (T2D) mortality. We aim to investigate the changes in miR-21, miR-122, miR-33a and miR-3064-5p in circulation and the liver of ApoE-/- mice with streptozocin (STZ)-induced T2D. Twenty 5-week-old male ApoE-/- mice were randomly assigned to the control (n = 10) and T2D group (n = 10) and intraperitoneally injected with a citrate buffer and streptozotocin (STZ) (40 mg/kg BW) once a day for three consecutive days. The successfully STZ-induced T2D mice (n = 5) and control mice (n = 5) were then fed with a high-fat diet (HFD) for 34 weeks. Compared to the control mice, ApoE-/- mice with STZ-induced T2D had slower (p < 0.05) growth, increased (p < 0.05) total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C), decreased (p < 0.05) high-density lipoprotein cholesterol (HDL-C) in serum, reduced (p < 0.05) TC and sterol regulatory element-binding protein-2 (Srebp-2), elevated (p < 0.05) ATP-binding-cassette-transporter-A1 (Abca1) in the liver, aggravated (p < 0.05) atherosclerotic lesions in the aorta, downregulated (p < 0.05) miR-21 and miR-33a, and upregulated (p < 0.05) miR-122 and miR-3064-5p in serum and the liver. In addition, the aortic lesions showed a positive correlation with miR-122 (r = 1.000, p = 0.001) and a negative correlation with miR-21 (r = −1.000, p = 0.001) in ApoE-/- mice with T2D. In conclusion, T2D-accelerated atherosclerosis correlates with a reduction in miR-21 and miR-33a and an elevation in miR-122 and miR-3064-5p in circulation and the liver of ApoE-/- mice.

LncRNA NEAT1/miR-146a-5p Axis Restores Normal Angiogenesis in Diabetic Foot Ulcers by Targeting mafG

“…The levels of miR-146a-5p were high in chronic DFU subjects compared to their acute counterparts, and in endothelial cells exposed to HGM in vitro compared to the control. This finding is in line with other reports where higher levels of miR-146a were reported in DFU and atherosclerosis cases [ 39 , 40 , 41 ]. Contradictory to our data, a lowered expression of miR-146a was assessed which was seen to delay healing response in diabetic mice [ 42 ]; however, few studies have suggested miR-146a as inflammation-inducible miRNA in various disease conditions [ 43 , 44 , 45 ].…”

Gut Microbiota Plays Essential Roles in Soyasaponin's Preventive Bioactivities against Steatohepatitis in the Methionine and Choline Deficient (MCD) Diet‐Induced Non‐Alcoholic Steatohepatitis (NASH) Mice

“…RNA Isolation, cDNA Synthesis, and Real-Time Fluorescent Quantitative PCR: Preparation of total RNA, cDNA synthesis, and qPCR were performed as described previously. [84] Briefly, total RNA was extracted from the liver and small intestine tissues using the TRIZOL reagent (Invitrogen, USA). Aliquots of 0.5 μg RNA were reversely transcribed to cDNA using the PrimeScript RT reagent kit (Takara, China).…”