MicroRNA-128 mimics ameliorated homocysteine-induced functional injury, apoptosis, and oxidative stress in rat cardiac microvascular endothelial cells by negatively regulating IRS1 expression.
miR-128 protects cardiac microvascular endothelial cells from homocysteine-induced injury by targeting IRS1 and reducing oxidative stress.
OBJECTIVE: Cardiac microvascular endothelial cells (CMECs) play a critical role in the physiological regulation of coronary blood flow and its dysfunction is associated with myocardium ischemic injury. This study was performed to clarify the effect of microRNA-128 (miR-128) on the CMEC injury in coronary heart disease (CHD) by binding to insulin receptor substrate 1 (IRS1). METHODS: The rat CMECs were cultured by explant culture method and identified by CD31 immunofluorescence assay. CMECs were treated with homocysteine (Hcy), which underwent stress of CHD, followed by treatment of miR-128 mimics/inhibitors or IRS1 siRNA. Expression of miR-128, IRS1, and vascular endothelial growth factor (VEGF) was determined. The viability, apoptosis, migration ability, and tube formation ability of CMECs were evaluated. The superoxide dismutase (SOD), malondialdehyde (MDA), and reactive oxygen species (ROS) of CMECs were evaluated, respectively. RESULTS: In rat CMECs, miR-128 was poorly expressed and IRS1 was highly expressed. Notably, miR-128 targeted and negatively regulated IRS1. Additionally, the treatment with Hcy in CMECs led to reduced viability, migration ability, tube formation, VEGF expression, SOD activity as well as increased cell apoptosis, MDA and ROS levels. The experimental results demonstrated that miR-128 mimics and IRS1 siRNA in rat CMECs promoted viability, migration ability, tube formation, VEGF expression, SOD activity, while repressing cell apoptosis, MDA and ROS levels. MiR-128 inhibitors could reverse the tendencies. CONCLUSION: Collectively, our study provides evidence that miR-128 targeted and negatively regulated IRS1 expression, whereby the functional injury of CMECs induced by Hcy was ameliorated. Furthermore, protection of miR-128 was stimulated by reducing oxidative stress.
Yan et al. (Wed,) conducted a other in Coronary heart disease. miR-128 mimics or IRS1 siRNA vs. Homocysteine treatment alone or miR-128 inhibitors was evaluated on Cell viability, apoptosis, migration ability, tube formation, and oxidative stress markers. MicroRNA-128 mimics ameliorated homocysteine-induced functional injury, apoptosis, and oxidative stress in rat cardiac microvascular endothelial cells by negatively regulating IRS1 expression.
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