Identification of miR‑145 as a regulator of the cardiomyocyte inflammatory response and oxidative stress under hyperglycemia

Abstract

The current study aimed to explore the effects of microRNA (miR)-145 on the inflammatory response and oxidative stress (OS) in high glucose (HG)-induced cardiomyocytes, as well as the specific mechanism underlying this action. H9c2 cells were treated with 33 mmol/l glucose (HG group) or cotreated with 24.5 mmol/l mannitol and 5.5 mmol/l glucose (hypertonic group), and the expression levels of miR-145 and ADP ribosylation factor 6 (ARF6) were detected. The cells were transfected with pcDNA3.1-ARF6, miR-145 mimics or corresponding negative controls prior to the assessment of cell survival rate. Levels of lactate dehydrogenase (LDH), reactive oxygen species (ROS) and malondialdehyde (MDA), as well as the activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx), and the levels of IL-6, TNF-α and monocyte chemoattractant protein-1 (MCP-1) were subsequently determined. The apoptotic rate of H9c2 cells was examined by flow cytometry. The interaction between miR-145-ARF6 was predicted and confirmed by luciferase reporter assays. In the HG group, miR-145 expression was significantly decreased and ARF6 expression significantly increased compared with controls. Furthermore, the levels of inflammatory factors (IL-6, TNF-α and MCP-1), LDH, ROS and MDA were significantly elevated in the HG group compared with controls. Significantly decreased SOD, CAT and GPx activities and significantly increased numbers of apoptotic cells were observed in the HG group compared with controls. The cells transfected with miR-145 mimics exhibited significantly decreased LDH, ROS and MDA levels, significantly increased antioxidant enzyme activities and significantly decreased apoptotic rates compared with controls, while the opposite results were observed in cells transfected with pcDNA3.1-ARF6. Moreover, co-transfection with miR-145 mimics and pcDNA3.1-ARF6 exacerbated the inflammatory response and OS injury in HG-induced cardiomyocytes compared with cells transfected with miR-145 mimics alone. Furthermore, miR-145 negatively targeted ARF6. miR-145 attenuated the HG-induced inflammatory response and OS injury in cardiomyocytes by negatively regulating ARF6, which may contribute to providing a theoretical basis for the treatment of diabetic cardiomyopathy.

Exosomal microRNAs miR-30d-5p and miR-126a-5p Are Associated with Heart Failure with Preserved Ejection Fraction in STZ-Induced Type 1 Diabetic Rats

“…We selected 12 miRNAs associated with diabetic HF. The initial selection of miRNAs in our panel were miR-1 [ 28 , 29 ], miR-21 [ 30 ], miR-29a [ 31 ], miR-30d [ 32 , 33 ], miR-34a [ 34 ], miR-126a [ 35 ], miR-143 [ 36 ], miR-145 [ 37 ], miR-195 [ 38 ], miR-206 [ 39 ], miR-320 [ 39 ] and miR-378 [ 40 ]. We found that the expression of all miRNAs was significantly lower in HFpEF diabetic hearts than in controls ( Figure 5 A–L).…”

Effect of miR-145 on intracardiac thrombosis in patients with rheumatic heart disease complicated with atrial fibrillation: A retrospective analysis

“…For example, inhibition of miR-155-5p could reduce the level of IL-6 in heart valves and serum in RHD patients and reduce valve inflammation and fibrosis induced by RHD. [ 21 , 22 ] Previous studies have demonstrated the antioxidant and anti-inflammatory effects of miR-145, [ 23 ] such as the downregulation of miR-145-5p expression in left and right atrial appendages in patients with rheumatic mitral valve disease. [ 8 ] A correlation between miR-145 and IL-6 was also reported.…”

Recent Update on the Molecular Mechanisms of Gonadal Steroids Action in Adipose Tissue

“…A correlation between the expression level of miR-222, the estrogen receptor and GLUT4 has also been demonstrated [265]. microRNAs which expression can be regulated by androgens (miR-124 and miR-145) and estrogens (miR-30c) are implicated in thermogenesis regulation by targeting MCT1, LDH and RIP140, respectively [266][267][268]. MCT1 expression is also modulated by miR-342-3p [269].…”