Abstract
This study aimed to investigate the role of miR‐138 in human coronary artery endothelial cell (HCAEC) injury and inflammatory response and the involvement of the PI3K/Akt/eNOS signalling pathway. Oxidized low‐density lipoprotein (OX‐LDL)‐induced HCAEC injury models were established and assigned to blank, miR‐138 mimic, miR‐138 inhibitor, LY294002 (an inhibitor of the PI3K/Akt/eNOS pathway), miR‐138 inhibitor + LY294002 and negative control (NC) groups. qRT‐PCR and Western blotting were performed to detect the miR‐138, PI3K, Akt and eNOS levels and the protein expressions of PI3K, Akt, eNOS, p‐Akt, p‐eNOS, Bcl‐2, Bax and caspase‐3. ELISAs were employed to measure the expressions of TNF‐α, IL‐4, IL‐6, IL‐8, IL‐10 and nitric oxide (NO) and the activities of lactate dehydrogenase (LDH) and eNOS. MTT and flow cytometry were performed to assess the proliferation and apoptosis of HCAECs. Compared to the blank group, PI3K, Akt and eNOS were down‐regulated in the miR‐138 mimic and LY294002 groups but were up‐regulated in the miR‐138 inhibitor group. The miR‐138 mimic and LY294002 groups showed decreased concentrations of TNF‐α, IL‐6, IL‐8 and NO and reduced activities of LDH and eNOS, while opposite trends were observed in the miR‐138 inhibitor group. The concentrations of IL‐4 and IL‐10 increased in the miR‐138 mimic and LY294002 groups but decreased in the miR‐138 inhibitor group. The miR‐138 mimic and LY294002 groups had significantly decreased cell proliferation and increased cell apoptosis compared to the blank group. These findings indicate that up‐regulation of miR‐138 alleviates HCAEC injury and inflammatory response by inhibiting the PI3K/Akt/eNOS signalling pathway.
Highlights
Endothelial cells, a single layer of cells that line the inner surface of blood vessels in the human body, inhibit activation of pro-inflammatory and clotting factors in vessels [1]
Compared with the blank group, PI3K, Akt and endothelial nitric oxide synthase (eNOS) mRNA expressions were up-regulated in the miR-138 inhibitor group but were down-regulated in the miR-138 mimic and LY294002 groups, and there was no significant difference between the miR-138 mimic and LY294002 groups (P > 0.05)
This study explored the roles of miR-138 and the PI3K/Akt/eNOS signalling pathway in human coronary artery endothelial cell (HCAEC) injury and inflammatory response
Summary
Endothelial cells, a single layer of cells that line the inner surface of blood vessels in the human body, inhibit activation of pro-inflammatory and clotting factors in vessels [1]. The loss of endothelial integrity results in several vascular complications, and endothelial cell injury and proliferative dysfunction have been shown to initiate the development of atherosclerosis [1]. Chronic vascular inflammation due to a persistent increase in circulating inflammatory cytokines is associated with endothelial dysfunction, which results in the development of atherosclerosis and cardiovascular disease [3]. It is important to identify the cellular and molecular mechanisms underlying endothelial cell injury and inflammatory response to develop new biomarkers and novel therapeutic strategies for endothelial cell injury. By modulating the expression of target genes, miRNAs can influence different biological processes, such as the cell cycle, proliferation, differentiation, survival and apoptosis [5, 6]. Recent studies have reported that miRNAs regulate endothelial cell apoptosis and senescence-related pro-inflammatory status [7, 8]. MiR-138 is an important member of a 2017 The Authors
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