RESUMO
Backgroud The present study aimed to investigate the function and regulatory mechanisms of lncRNA KCNQ1OT1 in vascular smooth muscle cells under oxidation low lipoprotein stimulation. Methods RNA sequencing was used to detect transcriptome changes of vascular smooth muscle cells treated with oxidation low lipoprotein. KCNQ1OT1, miR-196a-5p, and FOXO1 expression levels in VSMCs after oxidation low lipoprotein treatment were assessed using qRT-PCR and western blotting. RNA immunoprecipitation, RNA pull-down, and dual-luciferase reporter assay were used to confirm the interaction among lncRNA KCNQ1OT1, miR-196a-5p, and FOXO1. The functions of KCNQ1OT1, miR-196a-5p, and FOXO1 were analyzed by CCK-8 and flow cytometry. The serum samples of high fat-feeding mice and atherosclerosis patients were collected, and the levels of KCNQ1OT1 and miR-196a-5p were analyzed. Results In vitro expression of KCNQ1OT1 and FOXO1 decreased in VSMCs treated with oxidation low lipoprotein, accompanied by overexpression of miR-196a-5p. As a ceRNA, KCNQ1OT1 positively regulated FOXO1 and imparted a negative regulatory effect on miR-196a-5p. Interference KCNQ1OT1/miR-196a-5p/FOXO1 could change roliferation/apoptosis imbalance in VSMCs under oxidation low lipoprotein stimulation. Higher levels of KCNQ1OT1 and lower levels of miR-196a-5p can be found in the thoracic aorta tissues of high fat-feeding mice and serum samples from individuals with carotid atherosclerosis. Conclusion Aberrant expression of KCNQ1OT1/miR-196a-5p/FOXO1 pathway mediated oxidation low lipoprotein-induced proliferation/apoptosis imbalance in VSMCs.
Assuntos
MicroRNAs , RNA Longo não Codificante , Animais , Apoptose , Proliferação de Células , Proteína Forkhead Box O1/genética , Proteína Forkhead Box O1/metabolismo , Lipoproteínas LDL/metabolismo , Lipoproteínas LDL/farmacologia , Camundongos , MicroRNAs/genética , MicroRNAs/metabolismo , Músculo Liso Vascular/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismoRESUMO
BACKGROUND: microRNA-mRNA axes that are involved in oxidized low-density lipoprotein (ox-LDL)-induced vascular smooth muscle cells (VSMCs) proliferation/apoptosis imbalance need to be further investigated. OBJECTIVE: To investigate the functional role of miR-183-5p/FOXO1 in VSMCs and its interaction with ox-LDL. METHODS: RNA sequencing was used to detect transcriptome changes of VSMCs treated with ox-LDL. miR-183-5p and FOXO1 expression levels in VSMCs after ox-LDL treatment were assessed using qRT-PCR and western blotting. The regulatory effect of miR-183-5p on FOXO1 has been tried to prove using a dual-luciferase reporter assay. The functions of miR-183-5p, and FOXO1 were analyzed by CCK-8 assay and flow cytometry assay. The tissue samples or serum samples of high fat-feeding mice and carotid atherosclerosis patients were collected, and the levels of miR-183-5p/FOXO1 were analyzed. RESULTS: RNA sequencing data showed 81 miRNAs including miR-183-5p was significantly changed after ox-LDL treatment in VSMCs. FOXO1, a miR-183-5p's potential target, was also down-regulated in ox-LDL treated cells. qRT-PCR and western blot found that expression of FOXO1 mRNA and protein significantly reduced in VSMCs treated with ox-LDL, accompanied by overexpression of miR-183-5p. miR-183-5p inhibited FOXO1 mRNA by binding to its 3' UTR. Interference miR-183-5p/FOXO1 could change proliferation/apoptosis imbalance in VSMCs under ox-LDL stimulation. Higher levels of miR-183-5p but reduced FOXO1 can be found in the thoracic aorta tissues of high fat-feeding mice. In serum samples from individuals with carotid atherosclerosis, Higher levels of miR-183-5p were observed. the miR-183-5p level was positively related to the level of serum ox-LDL in patients. CONCLUSIONS: Aberrant expression of miR-183-5p/FOXO1 pathway mediated ox-LDL-induced proliferation/apoptosis imbalance in VSMCs. The miR-183-5p/FOXO1 axis can potentially be utilized as the target in the treatment of patients with atherosclerosis.
Assuntos
Doenças das Artérias Carótidas , MicroRNAs , Animais , Apoptose/genética , Doenças das Artérias Carótidas/metabolismo , Movimento Celular/genética , Proliferação de Células/genética , Proteína Forkhead Box O1/genética , Proteína Forkhead Box O1/metabolismo , Proteína Forkhead Box O1/farmacologia , Humanos , Lipoproteínas LDL/metabolismo , Camundongos , MicroRNAs/metabolismo , Músculo Liso Vascular/metabolismo , RNA Mensageiro/metabolismo , Transdução de SinaisRESUMO
Cardiovascular disease is a common chronic disease in the medical field, which has a great impact on the health of Chinese residents (especially the elderly). At present, the effectiveness of the prevention and treatment of cardiovascular diseases in my country is not optimistic. Overall, the prevalence and mortality of CVD are still on the rise. The timely and effective detection and treatment of cardiovascular and cerebrovascular diseases are of great practical significance to improve the health of residents and to carry out prevention and treatment. This article aims to study the application of ultrasound-based virtual reality technology in the diagnosis and treatment of cardiovascular diseases to improve the efficiency and accuracy of the diagnosis of cardiovascular and cerebrovascular diseases by medical staff. The focus is on the application of feature attribute selection related algorithms and classification related algorithms in medical and health diagnosis systems, and a cardiovascular and cerebrovascular disease diagnosis system based on naive Bayes algorithm and improved genetic algorithm is designed and developed. The system builds a diagnostic model for cardiovascular and cerebrovascular diseases and diagnoses and displays the corresponding results based on the patient's examination data. This paper first puts forward the theoretical concepts of ultrasonic virtual reality technology, scientific computing visualization, genetic algorithm, naive Bayes algorithm, and surgery simulation system and describes them in detail. Then, we construct a three-dimensional ultrasonic virtual measurement system, from the collection and reconstruction of image data to the filtering and segmentation of image data, plus the application of three-dimensional visualization and virtual reality technology to construct a three-dimensional measurement system. The experimental results in this paper show that 10 isolated congenital heart disease models with atrial septal defect (ASD) established through the use of three-dimensional visualization and virtual reality technology measured the short diameter, long diameter, and area of the atrial septal defect in the left and right atria. Finally, a value of L less than 0.05 indicates that the statistics are meaningful, and a value of r generally greater than 0.9 indicates that the virtual measurement result is highly correlated with the real measurement result.
Assuntos
Doenças Cardiovasculares , Comunicação Interatrial , Realidade Virtual , Idoso , Teorema de Bayes , Doenças Cardiovasculares/diagnóstico por imagem , Doenças Cardiovasculares/terapia , Humanos , UltrassonografiaRESUMO
PURPOSE: This study aimed to investigate the effect of adipose-derived stem cell (ADSC) transplantation on atherosclerosis (AS) and its underlying mechanisms. MATERIALS AND METHODS: In our study, rat AS model was established, and ADSCs were isolated and cultured. Atherosclerotic plaque and pathological symptoms of thoracic aorta were measured by Oil Red O staining and Hematoxylin-Eosin staining, respectively. Total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) levels were measured by an automatic biochemical analyzer. Expressions of vascular endothelial growth factor (VEGF), vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), aortic endothelin-1 (ET-1), interleukin-6 (IL-6), c-reactive protein (CRP), and tumor necrosis factor α (TNF-α) were measured by enzyme linked immunosorbent assay, VEGF, VCAM-1, ICAM-1, ET-1, respectively, and NF-κB p65 mRNA expressions were detected by quantitative real-time polymerase chain reaction. Protein expressions of VEGF, VCAM-1, ICAM-1, ET-1, NF-κB p65, p-NF-κB p65, and IκBα were measured by western blot. Moreover, NF-κB p65 expression was measured by immunofluorescence staining. RESULTS: ADSC transplantation alleviated the pathological symptoms of aortic AS. ADSC transplantation decreased the levels of TC, TG, and LDL-C and increased serum HDL-C level. Meanwhile, ADSC transplantation decreased the levels of IL-6, CRP, and TNF-α in AS rats. Moreover, the expressions of VEGF, ET-1, VCAM-1, and ICAM-1 were decreased by ADSC transplantation. ADSC transplantation inhibited phosphorylation of NF-κB p65 and promoted IκBα expression in AS rats. CONCLUSION: Our study demonstrated that ADSC transplantation could inhibit vascular inflammatory responses and endothelial dysfunction by suppressing NF-κB pathway in AS rats.