RESUMO
Atherosclerosis (AS) is the main aetiology of coronary heart disease, cerebral infarction and peripheral vascular disease in humans. Long-noncoding RNA (LincRNA)-p21 has been reported to participate in the development of AS. Therefore, this study was designed to investigate the mechanism of LincRNA-p21 on suppressing the development of AS. We fed ApoE-/- mice with a high-fat diet to induce an AS mouse model where the lesion area of AS and the extent of lipid deposition were measured. The binding of LincRNA-p21 and miR-221 or miR-221 and SIRT1 was measured using a dual luciferase reporter gene assay and RIP. Following loss- and gain- function assays, CCK8, EdU, Transwell assay and scratch test were performed to determine the biological processes of human aortic endothelial cells (HAECs). miR-221 was highly expressed while SIRT1 was poorly expressed in AS. LincRNA-p21 acted as a sponge for miR-221. miR-221 targeted and negatively regulated the expression of SIRT1. LincRNA-p21 promoted the deacetylation of Pcsk9 by SIRT1 by competitively binding to miR-221, whereby promoting HAEC proliferation, migration and tube formation. In conclusion, LincRNA-p21 acted as a molecular sponge for miR-221 to promote deacetylation of the promoter region of Pcsk9 by SIRT1, therefore preventing the development of AS.
Assuntos
Aterosclerose/genética , MicroRNAs/genética , Pró-Proteína Convertase 9/genética , RNA Longo não Codificante/genética , Sirtuína 1/genética , Idoso , Animais , Aterosclerose/metabolismo , Aterosclerose/patologia , Linhagem Celular , Movimento Celular/genética , Proliferação de Células/genética , Modelos Animais de Doenças , Feminino , Regulação da Expressão Gênica , Genes Reporter , Humanos , Masculino , Camundongos , Camundongos Knockout , Pessoa de Meia-Idade , Pró-Proteína Convertase 9/metabolismo , Interferência de RNA , Sirtuína 1/metabolismoRESUMO
This study investigated the functional role of p53-lincRNA-p21 in atherosclerosis (AS) by mediating the microRNA-17-5p (miR-17-5p)/SIRT7 axis. Peripheral blood was collected from AS patients, and an ApoE-/- mouse model of AS (AS-M) was induced by high-fat diet. The relationship among p53, lincRNA-p21, miR-17-5p, and SIRT7 was validated, and their effects on AS progression and vascular smooth muscle cell (VSMC) functions were analyzed using gain- and loss-of-function experiments in AS mice and human and mouse VSMCs. p53, lincRNA-p21, and SIRT7 were downregulated, and miR-17-5p was upregulated in AS-M and peripheral blood of AS patients. p53 positively regulated lincRNA-p21, while miR-17-5p, reversely targeted by lincRNA-p21, could target SIRT7. Overexpressing p53, lincRNA-p21, or SIRT7 contributed to impaired proliferation and promoted apoptosis of VSMCs in vitro as well as reducing the vulnerable plaque and lipid accumulation in AS mice. Collectively, p53-dependent lincRNA-p21 expression downregulated miR-17-5p, which consequently protecting against AS progression via SIRT7 elevation. Graphical abstract Collectively, p53-dependent lincRNA-p21 expression downregulated miR-17-5p, whichconsequently protecting against AS progression via SIRT7 elevation.
Assuntos
Apoptose , Aterosclerose/enzimologia , Proliferação de Células , MicroRNAs/metabolismo , Músculo Liso Vascular/enzimologia , Miócitos de Músculo Liso/enzimologia , RNA Longo não Codificante/metabolismo , Sirtuínas/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Idoso , Animais , Aterosclerose/genética , Aterosclerose/patologia , Estudos de Casos e Controles , Modelos Animais de Doenças , Feminino , Humanos , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout para ApoE , MicroRNAs/genética , Pessoa de Meia-Idade , Músculo Liso Vascular/patologia , Miócitos de Músculo Liso/patologia , RNA Longo não Codificante/genética , Transdução de Sinais , Sirtuínas/genética , Proteína Supressora de Tumor p53/genética , Regulação para CimaRESUMO
Stent implantation is the common treatment method for iliac vein (IV) occlusion. IV stents usually enter into the inferior vena cava (IVC) to partially or completely cover the contralateral IV, but it is still uncertain whether this can increase the risk of thrombosis in the contralateral IV. The purpose of this study was to investigate the effect of the stent position on the bilateral IVs patency. A total of 261 patients with symptomatic IV lesions, including 177 patients with non-thrombotic iliac vein lesions (NIVLs) and 84 patients with thrombotic iliac vein lesions (TIVLs), were implanted with IV stents between July 2007 and June 2017. The data of these patients were retrospectively studied. The follow-up time was 6-114 months, and the median time was 62 months. A total of 183 cases had stenting into the IVC for more than 5 mm. The incidence of thrombosis in the contralateral IV was only 0.55% (1/183). A total of 17 short- and long-term cumulative cases had ipsilateral thrombosis on the stent side. There was no significant difference between the incidence of patients (8.79%, 7/78) with stenting into the IVC for less than 5 mm and those with more than 5 mm (5.46%, 10/183, P = 0.287). However, in the TIVLs group, the incidence of ipsilateral thrombosis between stenting positions less than 5 mm (29.6%, 8/27) and those more than 5 mm (8.77%, 5/57) was significantly different (P = 0.022). Stent implantation for NIVLs had an excellent long-term patency rate; the primary patency rate and the assisted primary patency rate were 97.7% and 100%, respectively. The entry of IV stents into the IVC was safe and had a very low incidence of thrombosis in the contralateral vein. Stenting less into the IVC increased the incidence of thrombosis in the ipsilateral vein, especially among thrombotic cases. Treatment of NIVLs using stent implantation had a better long-term patency rate. This principle plays an important guiding role in the endovascular therapy of IV lesions.
Assuntos
Veia Ilíaca/cirurgia , Stents , Trombose/cirurgia , Adulto , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Veia Cava Inferior/cirurgiaRESUMO
OBJECTIVE: A retrograde technique through the gap between the distal stent landing zone and the iliac artery wall has been applied to treat type II endoleak after endovascular aortic aneurysm repair (EVAR). In this study, we tried to investigate its efficacy in the management of type III endoleak and intraoperative accidental events. METHODS: We reported 2 complications of EVAR that were difficult to treat with conventional methods. One patient had a sustained type III endoleak after EVAR, and the right renal artery was accidentally sealed by a graft stent in the other patient during the operation. RESULTS: Both complications were managed by the retrograde technique from the distal stent landing zone. In the first case, the endoleak was easily embolized by the retrograde catheterization technique, and in the second case, a stent was implanted in the right renal artery using the retrograde technique to restore blood flow. CONCLUSION: In some EVAR cases, the technique of retrograde catheterization through the distal stent-graft landing zone is feasible, safe, and easy to perform.