MicroRNA‐150 restores endothelial cell function and attenuates vascular remodeling by targeting PTX3 through the NF‐κB signaling pathway in mice with acute coronary syndrome

Abstract

MicroRNAs (miRNAs) have been known to function as important regulators in the vascular system, with various physiopathological effects such as vascular remodeling and hypertension modulation. We aimed to explore whether microRNA-150 (miR-150) regulates endothelial cell function and vascular remodeling in acute coronary syndrome (ACS), and the involvement of PTX3 and NF-κB signaling pathway. Ten normal mice and sixty ApoE mice were chosen, and their coronary artery tissues and endothelial cells were extracted. ApoE mice were injected with a series of inhibitor or mimic for miR-150, or siRNA against PTX3. The miR-150 expression, NF-κB1, RELA, and PTX3 mRNA expression were assessed by reverse transcription quantitative polymerase chain reaction, and pentraxin-3, p-P50, and p-P65 protein expression by Western blot analysis. Cell viability and migration were assessed by MTT assay and scratch test. Matrigel tube formation assay was employed to determine vascular remodeling of endothelial cells. The dual-luciferase reporter assay verified that PTX3 was a target of miR-150. Mice with ACS presented with decreased miR-150 but increased PTX3. It was observed that the miR-150 mimic and siRNA against PTX3 reduced levels of PTX3, NF-κB1, and RELA in mice, and the miR-150 inhibitor reversed the tendency. The in vitro cell experimentation proved that miR-150 might facilitate endothelial cell proliferation, migration, and restrain vascular remodeling via inhibiting PTX3 expression. On the basis of the results of this study, it was hypothesized that miR-150 could possibly maintain endothelial cell function and suppress vascular remodeling by inhibiting PTX3 through the NF-κB signaling pathway in mice with ACS.

Association of plasma pentraxin 3 concentration with angiographic and clinical outcomes in patients with acute ST‐segment elevation myocardial infarction treated by primary angioplasty

“…22 In animal models, the inflammatory response related to the release of PTX3 regulated by identified microRNAs (microRNA-224 and microRNA-150). 23,24 The linear correlation between leukocyte count and PTX3 concentration found in our study (r = .21, p < .001) supports previous finding that PTX3 attenuates leukocyte recruitment at the site of inflammation. 25 It is unclear whether use of anti-inflammatory drugs or gene targeting therapy with the aim of reducing the PTX3 concentration may improve the angiographic and clinical outcome of patients with STEMI undergoing primary PCI, or, in contrast, it may be harmful to inhibit the immunity-inflammatory reactions associated with PTX3 release in patients with AMI.…”

Long noncoding RNA MALAT1 contributes to pregnancy‐induced hypertension development by enhancing oxidative stress and inflammation through the regulation of the miR‐150‐5p/ET‐1 axis

“…Existing evidence also supports the notion that miR‐150 expression is significantly repressed in plasma from patients with pulmonary arterial hypertension 27 . In addition, miR‐150 can restore EC function and attenuate vascular remodeling through the NF‐κB pathway in mice with acute coronary syndrome 28 . A previous study in preeclamptic female depicted significantly higher expression of ET‐1 in the plasma of preeclamptic patients 29 .…”

Changes in circulating microRNA and arterial stiffness following high‐intensity interval and moderate intensity continuous exercise

“…Additionally, ci‐miRs‐ 150‐5p, 155‐5p, and 181b‐5p increased following HII exercise, while only ci‐miR‐150‐5p also increased in response to MOD exercise. MiRs‐ 150, 155, and 181b are anti‐inflammatory via indirect regulation of NF‐kB (Cheng, Njock, Khyzha, Dang, & Fish, 2014; Luo et al., 2018). MiR‐155 may also have pro‐inflammatory effects, and acts to regulate smooth muscle cell function by directly targeting eNOS and angiotensin II type I receptor expression (Sun et al., 2012; Yang et al., 2014; Zhang, Zhao, Yu, Lu, & Zheng, 2015).…”