RESUMO
Type III redundancy of the foramen ovale flap (RFOF) mimics hemodynamic changes of mitral stenosis(MS), which has not been particularly highlighted in previous literature but carries a favorable prognosis.
Assuntos
Hemodinâmica , Estenose da Valva Mitral , Humanos , Estenose da Valva Mitral/fisiopatologia , Estenose da Valva Mitral/cirurgia , Hemodinâmica/fisiologia , Diagnóstico Diferencial , Feminino , Forame Oval/fisiopatologia , Forame Oval/diagnóstico por imagem , Ecocardiografia Transesofagiana/métodosRESUMO
Objective: Acute coronary syndrome (ACS) is the most dangerous and deadly form of coronary heart disease. Herein, we aimed to explore ACS-specific circulating lncRNAs and their regulatory mechanisms. Methods: This study collected serum samples from ACS patients and healthy controls for microarray analysis. Dysregulated circulating lncRNAs and mRNAs were determined with |log2fold - change| > 1 and p < 0.05. lncRNA-mRNA coexpression analysis was carried out. ENST00000538705.1 and ALOX15 expression was further verified in serum specimens. In human coronary artery endothelial cells (HCAECs), ENST00000538705.1 and ALOX15 were knocked out through transfecting specific siRNAs. Thereafter, proliferation and migration were investigated with CCK-8 and wound-healing assays. Myocardial infarction rat models were established and administrated with siRNAs against ENST00000538705.1 or ALOX15. Myocardial damage was investigated with H&E staining, and serum TC, LDL, and HDL levels were measured. Results: Microarray analysis identified 353 dysregulated circulating lncRNAs and 441 dysregulated circulating mRNAs in ACS. Coexpression analysis indicated the interaction between ENST00000538705.1 and ALOX15. RT-qPCR confirmed the remarkable upregulation of circulating ENST00000538705.1 and ALOX15 in ACS patients. In HCAECs, ENST00000538705.1 knockdown lowered the expression of ALOX15 but ALOX15 did not alter the expression of ENST00000538705.1. Silencing ENST00000538705.1 or ALOX15 weakened the proliferation and migration of HCAECs. Additionally, knockdown of ENST00000538705.1 or ALOX15 relieved myocardial damage, decreased serum TC and LDL levels, and elevated HDL levels in myocardial infarction rats. Conclusion: Collectively, our findings demonstrate that circulating ENST00000538705.1 facilitates ACS progression through modulating ALOX15, which provide potential targets for ACS treatment.
Assuntos
Síndrome Coronariana Aguda , Infarto do Miocárdio , RNA Longo não Codificante , Animais , Araquidonato 15-Lipoxigenase/genética , Araquidonato 15-Lipoxigenase/metabolismo , Células Endoteliais/metabolismo , Humanos , Infarto do Miocárdio/genética , Infarto do Miocárdio/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , RNA Mensageiro/genética , RNA Interferente Pequeno/metabolismo , RatosRESUMO
OBJECTIVE: Increasing evidence highlights the significance of microRNAs (miRNAs) in the progression of atherosclerosis (AS). Our aim was to probe out the role and regulatory mechanism of miR-29a-3p in AS. METHODS: An in vivo model of AS was conducted by high-fat diet ApoE-/- mice. Oxidized low-density lipoprotein- (ox-LDL-) exposed vascular smooth muscle cells (VSMCs) were utilized as an in vitro of AS. Serum levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were detected. Hematoxylin and eosin (H&E) and Masson's staining was presented to investigate the pathological changes. miR-29a-3p and TNFRSF1A expression was detected by RT-qPCR. Proliferative, migrated, and invaded abilities of VSMCs were determined via a series of assays. The interaction between miR-29a-3p and TNFRSF1A was verified through luciferase reporter assay. RESULTS: Upregulated miR-29a-3p and downregulated TNFRSF1A were found both in vitro and in vivo models of AS. miR-29a-3p mimic distinctly decreased the serum levels of TC, TG, and LDL-C and increased serum HDL-C levels. Moreover, its overexpression could ameliorate plaque formation of AS mice. In ox-LDL-induced VSMCs, miR-29a-3p overexpression notably decreased cell proliferation, migration, and invasion, which was reversed by TNFRSF1A overexpression. Also, miR-29a-3p could directly target the 3'UTR of TNFRSF1A. CONCLUSION: miR-29a-3p overexpression ameliorated plaque formation of AS and suppressed proliferation, migration, and invasion of ox-LDL-induced VSMCs via TNFRSF1A, which offered novel insights into the progression of AS.