Inhibition of XIST attenuates abdominal aortic aneurysm in mice by regulating apoptosis of vascular smooth muscle cells through miR-762/MAP2K4 axis.

Abdominal aortic aneurysm (AAA) is a common chronic aortic degenerative disease. Long non-coding RNA X-inactive specific transcript (XIST) is associated with the progression of AAA, while the underlying mechanism is still unclear. We investigated the functional role of XIST in AAA. AAA mouse model was established by administration of Angiotensin II (Ang II). Primary mouse vascular smooth muscle cells (VSMCs) were separated from the abdominal aorta of Ang II-induced AAA mice, and then treated with Ang II. XIST was highly expressed in Ang II-treated VSMCs. Cell proliferation ability was decreased and apoptosis was increased in VSMCs following Ang II treatment. XIST knockdown reversed the impact of Ang II on cell proliferation and apoptosis in VSMCs. XIST promoted mitogen-activated protein kinase kinase 4 (MAP2K4) expression by sponging miR-762. XIST overexpression suppressed cell proliferation and apoptosis of Ang II-treated VSMCs by regulating miR-762/MAP2K4 axis. Finally, Ang II-induced AAA mouse model was established to verify the function of XIST in AAA. Inhibition of XIST significantly attenuated the pathological changes of abdominal aorta tissues in Ang II-induced mice. The expression of miR-762 was inhibited, and MAP2K4 expression was enhanced by XIST knockdown in the abdominal aorta tissues of AAA mice. In conclusion, these data demonstrate that inhibition of XIST attenuates AAA in mice, which attributes to inhibit apoptosis of VSMCs by regulating miR-762/MAP2K4 axis. Thus, this study highlights a novel ceRNA circuitry involving key regulators in the pathogenesis of AAA.

Hsa_circ_0137008 suppresses the malignant phenotype in colorectal cancer by acting as a microRNA-338-5p sponge.

BACKGROUND: Circular RNAs (circRNAs) have been shown to play a crucial role in tumorigenesis. In this study, we investigated the function of hsa_circ_0137008 and its underlying molecular mechanism in colorectal cancer (CRC). METHODS: Gene expression was conducted by quantitative real-time PCR or western blot. Functional experiments were performed by cell count kit-8, colony formation assay, wound healing, and transwell assays. Luciferase reporter assay and RNA pull-down assay were performed to investigate the molecular mechanism of hsa_circ_0137008 in CRC. In addition, the xenograft tumor model was applied to determine the role of hsa_circ_0137008 in vivo. RESULTS: Downregulation of hsa_circ_0137008 was observed in CRC tissues and cell lines. Functionally, overexpression of hsa_circ_0137008 inhibited the proliferation of CRC cells, as indicated by the inhibition of proliferative protein expression (Ki67 and PCNA), reduced cell viability and colony formation ability. Upregulation of hsa_circ_0137008 suppressed the migration, invasion, and epithelial to mesenchymal transition (EMT) of CRC cells. Mechanically, hsa_circ_0137008 negatively regulated the expression of microRNA-338-5p (miR-338-5p). Furthermore, hsa_circ_0137008 abated the miR-338-5p mediated promotion on CRC cell progression. Tumor suppressive function of hsa_circ_0137008 was validated in vivo. CONCLUSION: These findings highlighted the fact that overexpression of hsa_circ_0137008 inhibited the progression of CRC via sponging miR-338-5p, suggesting that hsa_circ_0137008/miR-338-5p axis is a principal regulator of CRC tumorigenesis.

Mechanism and Management of Retrograde Type A Aortic Dissection Complicating TEVAR for Type B Aortic Dissection.

BACKGROUND: This study is to investigate the causes, treatment methods, and preventive measures of retrograde type A aortic dissection (RAAD) complicating thoracic endovascular aortic repair (TEVAR) for type B aortic dissection (TBAD). METHODS: From January 2005 to December 2013, 360 TBAD patients receiving TEVAR were enrolled in this study. Among them, 304 cases were male and 56 cases were female. They were from 19 to 85 years old, with a mean age of 52 ± 12.8 years old. The average follow-up time was 32 ± 11.3 months (3-63 months), the follow-up rate was 69.1% (249 cases), and the lost rate was 30.9% (111 cases). The reasons and the treatment methods of RAAD complicating TEVAR for TBAD were analyzed. RESULTS: There were 5 cases of RAAD complicating TEVAR in TBAD (1.4%) patients, among them, 4 cases were male and 1 case was female. TEVAR operation failed in 1 case because of RAAD occurrence during TEVAR. This case was treated with open operation. In the other 4 cases, TEVAR operation was successfully carried out. During follow-up, RAAD was found in 3 cases within 1 month after TEVAR and in 1 case at 1 year after TEVAR. Conservative treatment was applied to 2 cases, whereas surgical operation treatment was performed in the other 3 cases. One case of conservative treatment patient was dead, and the other 4 cases are still alive. CONCLUSIONS: Incomplete design of stent-graft system, rough handling and presence of vascular wall lesions are the main reasons of RAAD complicating TEVAR for TBAD. Surgical operation is the most effective treatment measure for RAAD complicating TEVAR for TBAD.

AhR regulates VEGF expression by promoting STAT1 transcriptional activity, thereby affecting endothelial angiogenesis in acute limb ischemia.

BACKGROUND: Angiogenesis has great potential in the treatment of acute limb ischemia (ALI). Here, we aimed to investigate the effect and mechanism of Aryl hydrocarbon receptor (AhR) on angiogenesis in ALI. METHODS: The ALI mouse model was constructed by femoral artery ligation, and the cell ischemia injury was induced by Hypoxia/serum deprivation. The laser doppler perfusion imaging was executed to detect the limb blood flow velocity. The tube formation assay was performed to evaluate angiogenesis. The cell viability was measured by 3-(45)-dimethylthiahiazo(-z-y1)-35-di-phenytetrazoliumromide. The cell migration was detected by wound healing assay. Hematoxylin-eosin, immunohistochemistry, immunofluorescence, dual-luciferase reporter gene assay, and Chromatin immunoprecipitation assay were conducted. RESULTS: In ALI models, AhR expression was increased and translocated from cytoplasm to nucleus. Besides, necrosis and inflammatory infiltration were also increased in gastrocnemius tissues of model mice. In addition, AhR loss (LV-sh-AhR) promoted cell viability, angiogenesis, and migration, and also elevated the levels of vascular endothelial growth factor (VEGF), Tie2, and Ang2 in HUVEC models with Hypoxia/serum deprivation injury. Meanwhile, the interaction between AhR and signal transducer and activator of transcription 1 (STAT1), as well as STAT1 and VEGF, has also been confirmed. Co-transfection of LV-sh-AhR and LV-STAT1 suppressed cell viability, angiogenesis, and migration of injured HUVECs. Furthermore, injection of AAV2/9-shAhR in vivo also promoted angiogenesis, which was consistent with the in vitro experimental results. CONCLUSIONS: In ALI models, activated AhR was translocated to the nucleus and down-regulated VEGF expression by promoting the transcriptional activity of STAT1, thereby inhibiting endothelial angiogenesis.

Application of transmesenteric vein extrahepatic portosystemic shunt in treatment of symptomatic portal hypertension with cavernous transformation of portal vein.

Purpose: To evaluate the feasibility and efficacy of a transmesenteric vein extrahepatic portosystemic shunt (TmEPS) for the treatment of cavernous transformation of the portal vein (CTPV). Materials and methods: The clinical data of 20 patients with CTPV who underwent TmEPS between December 2020 and January 2022 â€‹at Henan Provincial People's Hospital were retrospectively collected. The superior mesenteric vein (SMV) trunk was patent or partially occluded in these patients. An extrahepatic portosystemic shunt between the inferior vena cava and the SMV was established using a stent graft through an infraumbilical median longitudinal mini-laparotomy. The technical success, efficacy, and complication rates were evaluated, and the pre- and postoperative SMV pressures were compared. Patients' clinical outcomes and shunt patency were assessed. Results: TmEPS was successfully performed in 20 patients. The initial puncture success rate of the balloon-assisted puncture technique is 95%. The mean SMV pressure decreased from 29.1 â€‹± â€‹2.9 â€‹mmHg to 15.6 â€‹± â€‹3.3 â€‹mmHg (p â€‹< â€‹0.001). All symptoms of portal hypertension resolved. No fatal procedural complications occurred. During the follow-up period, hepatic encephalopathy occurred in two patients. The remaining patients remained asymptomatic. All shunts were patent. Conclusions: TmEPS is a feasible, safe, and effective treatment option for patients with CTPV.

Limb graft occlusion following endovascular aortic repair: Incidence, causes, treatment and prevention in a study cohort.

The present study investigated the incidence, causes, treatment and prevention of limb graft occlusion following endovascular aortic repair (EVAR). A total of 66 cases of abdominal aortic aneurysm receiving EVAR at our department from January 2005 to December 2013 were enrolled. After EVAR, patients received routine antiplatelet therapy of 75 mg PLAVIX for 6 months and then 100 mg Aspirin for another 6 months by oral administration. According to previous clinical experiences, antiplatelet therapy is able to effectively reduce the incidence of iliac occlusion after EVAR. A total of 61 bifurcated grafts and 5 aortauniilac grafts (127 limbs in total) were used. Physical examination, ankle-brachial-index and computer tomographic angiography were performed at 10 days, at 3, 6 and 12 months and annually thereafter. It was found that 7 limbs in 7 patients (10.6% of patients, 5.5% of limbs) were occluded between 20 days and 12 months (average, 7.8±5.3 months) after EVAR. Acute and severe ischemia was found in 2 cases, claudication was in found 3 cases, asthenia in both legs was found in 1 case and 1 case was asymptomatic. Femoral-femoral bypass, femoral-femoral bypass and stenting, aorto-iliac/femoral bypass, thrombectomy and conservative treatment were performed in 1 patient each and thrombectomy together with stenting was performed in 2 cases. Limb graft occlusion was not rare after EVAR. Treatment of this complication included surgery and endovascular therapy such as bypass, thrombectomy and thrombolysis. In conclusion, aggressive pre-emptive treatment including angioplasty and stenting prevented occlusion in certain cases.