Background: Atherosclerosis (AS) is a major risk factor for cardiovascular disease. microRNAs play a key role in gene regulation in the formation and development of atherosclerotic plaques. Herein, the role and target gene of miR-185 in AS were explored. Materials and methods: Cell viability, migration and invasion were examined by cell counting kit-8 (CCK-8) and transwell assay. The relative luciferase activity was measured by luciferase reporter assay. The levels of miR-185, STIM1, vascular endothelial growth factor (VEGF) and matrix metalloprotein-9 (MMP-9) were evaluated by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blot. Results: The results revealed that ox-LDL decreased miR-185 expression, and enhanced STIM1 expression in MOVAS cells, as well promoted cell viability, migration and invasion. 3ʹ-UTR of STIM1 contained miR-185 binding site according to the Targetscan. miR-185 silencing or STIM1 overexpression promoted the viability, migration and invasion of ox-LDL-induced MOVAS cells. miR-185 overexpression or STIM1 silencing had the opposite effect. Besides, miR-185 silencing upregulated the levels of VEGF and MMP-9 in vitro, and increased the lesions of arterial wall tissues and STIM1 positive rate in vivo. However, STIM1 silencing reversed these effects. Conclusions: Sum up, STIM1 was a potential target gene of miR-185 in AS. Knockdown of miR-185 facilitated the progression of AS through enhancing cell proliferation, migration and invasion via targeting STIM1. The research provides a novel view of miR-185/STIM1 axis function in AS development, and this targeting method may prevent and treat AS.
Angiogenesis is a vital biological mechanism representing the adaptive response to a variety of pathological stimuli such as hypoxia. It is regulated by several pro-angiogenic and anti-angiogenic microRNAs. Studies have demonstrated an altered microRNA-185 (miR-185) expression in endothelial cells under hypoxic conditions; however, its role in angiogenesis has not been elucidated. We investigated the role of miR-185 in angiogenesis and found that miR-185 had an inhibitory effect on cell proliferation, migration, and tube formation. Stromal interaction molecule 1 (STIM1) appeared to be a direct target of miR-185 by computational prediction; this was confirmed by luciferase reporter assay. Silencing of the STIM1 gene was found to mimic miR-185-mediated inhibition of angiogenesis. STIM1 overexpression eliminated the anti-angiogenic effect of miR-185. Our study results suggest a direct interaction between miR-185 and STIM1 mRNA in microvascular endothelial cells. MicroRNA-185 acted as a negative regulator of angiogenesis in microvascular endothelial cells through downregulation of the STIM1 protein.
Background. Heart failure is a critical health problem worldwide, and cardiac hypertrophy is an important characteristic of heart failure. Bromodomain-containing protein 4 (BRD4) is involved in various cellular processes, including cardiac hypertrophy. This study aimed to investigate the mechanism underlying the effects of BRD4 on cardiac hypertrophy. Methods. Rat myoblast H9c2 cells were treated with angiotensin II (Ang II) to increase the mRNA and protein expressions of BRD4. BRD4 was silenced by small interfering RNA (siRNA) in H9c2 cells. Proteins involved in Nrf2-HO-1 pathway were determined by Western blot. Results. Our data suggest that BRD4 silencing attenuated Ang II, increased the percentage of TUNEL + cells and caspase-3 activity, increased oxidative stress, and increased the expression and content of pro-inflammatory cytokines. Mechanistically, we found that BRD4 silencing enhanced the protein expressions of Nrf2 and HO-1 and inhibited the TLR4 and phosphorylation of NF-kappa B in Ang II-stimulated H9c2 cells. TLR4 overexpression attenuated cardioprotection against Ang II by BRD4 silencing, including cardiac hypertrophy, oxidative stress, and inflammatory cytokine production. Additionally, TLR4 overexpression attenuated an increase in Nrf2 and HO-1 proteins and decreased phosphorylated NF-kappa B in H9c2 cells. Conclusion. Our results speculate that the BRD4/TLR4 axis might be a promising strategy for treating cardiovascular diseases with cardiac hypertrophy, including HF.
<b><i>Objectives:</i></b> Angiotensin II (Ang II)-induced atrial fibrosis plays a vital role in the development of atrial fibrillation (AF). Lysyl oxidase-like 2 (LOXL2) plays an essential role in matrix remodeling and fibrogenesis, indicating it may involve fibrosis-associated diseases. This study aims to elucidate the role of LOXL2 in AF, and its specific inhibitor can suppress Ang II-induced inflammatory atrial fibrosis and attenuate the enhanced vulnerability to AF. <b><i>Methods:</i></b> Male mice C57BL/6 were subcutaneously infused with either saline or Ang II (2 mg/kg/day) for 4 weeks. DMSO or LOXL2 inhibitor LOXL2-IN-1 hydrochloride (LOXL2-IN-1) at a dose of 100 μg/kg/day were intraperitoneally injected once daily for 4 weeks. Morphological, histological, and biochemical analyses were performed. AF was induced by transesophageal burst pacing in vivo. <b><i>Results:</i></b> Expression of LOXL2 was increased in serum of AF patients and Ang II-treated mice. LOXL2-IN-1 significantly attenuated Ang II-induced AF vulnerability, cardiac hypertrophy, atrial inflammation, and fibrosis. LOXL2-IN-1 suppressed Ang II-induced expression of transforming growth factor beta-1 (TGF-β1) and collagen I and phosphorylation of Smad2/3 in atrial tissue. <b><i>Conclusions:</i></b> LOXL2 is a target of AF, and its inhibitor prevents atrial fibrosis and attenuated enhanced vulnerability to AF potentially through the TGF-β/Smad pathway.
Objective. To compare the efficacy of catheter ablation and medical therapy in patients with heart failure and atrial fibrillation. Methods. We searched randomized controlled trials comparing catheter ablation versus medical therapy for heart failure and atrial fibrillation through PubMed, MEDLINE, Embase, Cochrane Clinical Trials Database, Web of Science, and China National Knowledge Infrastructure. Articles were investigated for their methodological quality using the Cochrane Collaboration risk of the bias assessment tool. Forest plots, funnel plots, and sensitivity analysis were also performed on the included articles. Results were expressed as risk ratio (RR) and mean difference (MD) with 95% confidence intervals. Results. Nine (9) studies were included in this study with 1131 patients. Meta-analysis showed a reduction in all-cause mortality from catheter ablation compared with medical therapy (RR = 0.53, 95% CI = 0.37 to 0.76; P = 0.0007 ) and improved left ventricular ejection fraction (LVEF) (MD = 6.45, 95% CI = 3.49 to 9.41; P < 0.0001 ), 6-minute walking time (6MWT) (MD = 28.32, 95% CI = 17.77 to 38.87; P < 0.0001 ), and Minnesota Living with Heart Failure Questionnaire (MLHFQ) score (MD = 8.19, 95% CI = 0.30 to 16.08; P = 0.04 ). Conclusion. Catheter ablation had a better improvement than medical treatment in left ventricular ejection fraction, cardiac function, and exercise ability for atrial fibrillation and heart failure patients.
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