METTL14/YTHDF1 axis-modified UCHL5 aggravates atherosclerosis by activating the NLRP3 inflammasome.

BACKGROUND: Vascular smooth muscle cell (VSMC) phenotypic switching contributes to VSMC proliferation and migration in atherosclerosis (AS). Nevertheless, the regulatory mechanism of VSMC phenotypic switching during AS progression is unclear. Here, the role and regulatory mechanism of UCHL5 in VSMC phenotypic switching during AS progression were investigated. METHODS: ApoE-/- mice were fed with high fat diet to establish AS model in vivo. VSMCs stimulated by ox-LDL were used as AS cellular model. VSMC proliferation and migration were examined by CCK8 assay and transwell assay, respectively. The levels of pro-inflammatory cytokines were assessed using ELISA. The interactions between METTL14/YTHDF1, UCHL5 and NLRP3 were analyzed using RIP and/or dual-luciferase reporter gene and/or Co-IP assays. NLRP3 ubiquitination was analyzed by ubiquitination analysis. RESULTS: UCHL5 was significantly upregulated in AS patients and ox-LDL-treated VSMCs. UCHL5 silencing ameliorated plaque formation and vascular remodeling in vivo and suppressed ox-LDL-induced VSMC proliferation, migration, inflammation and phenotypic switching in vitro. Moreover, METTL14 could increase UCHL5 mRNA m6A level and promoted UCHL5 expression by recruiting YTHDF1. Moreover, UCHL5 overexpression enhanced protein stability by deubiquitinating NLRP3. Rescue studies revealed that NLRP3 overexpression abrogated UCHL5 silencing-mediated biological effects in ox-LDL-treated VSMCs. CONCLUSION: UCHL5 modified by METTL14/YTHDF1 axis could facilitate the inflammation and vascular remodeling in atherosclerosis by activating the NLRP3 inflammasome.

Sex-related differences in the effect of rotational thrombectomy for thrombus-containing lower limbs ischemic lesions.

BACKGROUND: To assess the immediate effect and factors affecting the efficacy of rotational thrombectomy (RT) in patients with thrombus-containing lower-limb ischaemic lesions. METHODS: Patients were retrospectively divided into two groups: RT and RT+ CDT (Catheter-directed thrombolysis). The RT group included patients in whom intraoperative thrombus aspiration was successful, while the RT + CDT group included patients in whom intraoperative thrombus aspiration was less effective and remedial CDT treatment was used. The primary outcome was the immediate effect of RT on thrombus-containing lower-limb ischaemic lesions. RESULTS: From May 2015 to July 2021, 170 patients (113 men, 57 women; mean age, 74.0 years) with thrombus-containing lower-limb ischaemic lesions were treated in our centre. Of these patients, 113 received RT only, while 57 received RT + CDT. There were no significant intergroup differences in terms of age, disease duration, or comorbidities, but a higher proportion of male patients and higher preoperative plasma D-dimer levels (1.23 vs. 0.84; p = .017) was observed in the RT + CDT group. There were no significant intergroup differences in terms of diagnosis, lesion characteristics, lesion location, or lesion length. Multivariate logistic regression analysis revealed that male sex (odds ratio [OR], 2.65; 95% confidence interval [CI], 1.098-6.410; p = .030) and poor distal runoff (OR, 2.94; 95% CI, 1.439-5.988; p = .003) were associated with higher rates of additional CDT. Male patients also had a significantly longer onset time, more thrombotic occlusions, and a greater frequency of in-stent restenosis. CONCLUSIONS: RT alone or with CDT is a feasible primary treatment option for thrombus debulking. Sex significantly influences the effect of RT on thrombus-containing lower-limb ischaemic lesions.

Diabetes Mellitus Lowers the Risk of Aortic Dissection: a Systematic Review and Meta-Analysis.

BACKGROUND: This systematic review and meta-analysis aimed to investigate the association between diabetes mellitus and aortic dissection. METHODS: The PubMed and Embase databases were searched until December 2019 to identify all articles reporting diabetes mellitus and aortic dissection. The pooled odds ratio and 95% confidence interval were calculated using random-effects model. RESULTS: A total of 14 articles with 15,794 participants, of which 2133 diabetes mellitus patients, were eligible and included in this meta-analysis. The data suggested that diabetes mellitus decreased the risk of aortic dissection. In the subgroup analysis, this association was significant in worldwide studies except for the Chinese cohort and in studies adjusted for confounding factors. The results were stable after sensitivity analysis and no evidence of publication bias was found among studies. CONCLUSIONS: The result of this meta-analysis indicated that diabetes mellitus was associated with a lower risk of aortic dissection.

Off-the-Shelf Devices for Treatment of Thoracic Aortic Diseases: Midterm Follow-up of TEVAR With Chimneys or Physician-Made Fenestrations.

Purpose: To evaluate the midterm outcomes of thoracic endovascular aortic repair (TEVAR) using chimney grafts (ch-TEVAR) or thoracic stent-grafts with fenestrations made on the back table (f-TEVAR) to treat thoracic aortic dissection (TAD) and thoracic aortic aneurysm (TAA). Materials and Methods: A retrospective analysis was conducted of 474 consecutive patients (mean age 62.3±10.7 years; 346 men) treated with either f-TEVAR (n=110) or ch-TEVAR (n=364) for 352 TADs (81 f-TEVAR and 271 ch-TEVAR) or 122 TAAs (29 f-TEVAR and 93 ch-TEVAR) from 2008 to 2016. The primary endpoints at 30 days and during follow-up were overall mortality, aorta-related mortality, and major complications. The secondary endpoints were endoleak and reintervention. The patency of the target branches, cost of hospitalization, and the use of antiplatelet drugs were also analyzed. Results: Intraoperative type I endoleaks were treated in 69 (14.6%) cases (4 f-TEVAR and 65 ch-TEVAR, p<0.01) to achieve 100% technical success. Four (0.8%) patients died within 30 days [1 (0.9%) f-TEVAR and 3 (0.8%) ch-TEVAR]. Perioperative cerebral ischemia (1 fatal stroke) occurred in 9 (1.9%) patients: (1 f-TEVAR and 8 ch-TEVAR, p=0.39). During the mean follow-up of 50.6±20.0 months (49.5±18.3 months in f-TEVAR and 50.9±20.6 months in ch-TEVAR), 11 (2.3%) patients died of an aorta-related event. Type I endoleak was present in 40 (8.4%) patients (1 f-TEVAR and 39 ch-TEVAR, p<0.01). Eleven (2.3%) patients experienced stent-graft migration and 13 (2.7%) had a retrograde dissection. One hundred (16.9%) of the 593 branch stents occluded (4/75 in the f-TEVAR group and 96/518 in the ch-TEVAR group, p<0.01). The branch reintervention rate was 7.2% (34/474). The f-TEVAR group had a significantly higher probability of freedom from branch occlusion (92%) than the ch-TEVAR group (83%, p=0.007). Conclusion: Off-the-shelf techniques employing chimney grafts and homemade fenestrations are both suitable options for TAD and TAA involving the supra-aortic branches, with a low incidence of reintervention. Fenestrated TEVAR seems to have more favorable short- and midterm outcomes. Further study of these off-the-shelf techniques for aortic arch repair is warranted.

Long-term outcome of sac filling with fibrin sealant after endovascular aneurysm repair of abdominal aortic aneurysm with challenging aortic neck anatomy.

OBJECTIVE: A retrospective single-center study is reported here to assess the safety and long-term effectiveness of applying a fibrin sealant (FS) sac-filling strategy to eliminate type IA endoleak (TIAE) after endovascular aneurysm repair (EVAR) of abdominal aortic aneurysm. METHODS: Characteristics of abdominal aortic aneurysm patients who had challenging proximal aortic neck anatomy (short or angulated) and underwent FS sac filling to resolve TIAE after traditional EVAR in Changhai Hospital between December 2006 and July 2010 were collected and reviewed. Intrasac pressure was measured with a preloaded catheter before and after FS filling to observe the immediate curative effect. The 7- to 10-year long-term effect was evaluated on the basis of the occurrence of endoleak, maximum aneurysm diameter, all-cause mortality, and other severe complications by annual aortic computed tomography angiography check. RESULTS: There were 107 patients with short (≤15 mm; 83/107 [77.6%]) or angulated (>60 degrees; 27/107 [25.2%]) aneurysm neck who underwent FS sac filling. The mean age of the patients was 71.1 ± 12.1 years (68 male patients). Of the 107 endoleaks, 106 (106/107 [99.1%]) were resolved, and 3 (3/107 [2.8%]) patients died in the perioperative period. Intrasac systolic, diastolic, mean, and pulse pressures decreased significantly in the treated cases (systolic pressure, 114.1 ± 16.7 mm Hg vs 59.5 ± 20.4 mm Hg; diastolic pressure, 65.0 ± 10.4 mm Hg vs 51.4 ± 18.2 mm Hg; mean pressure, 81.3 ± 11.4 mm Hg vs 54.1 ± 18.8 mm Hg; pulse pressure, 49.1 ± 12.8 mm Hg vs 8.2 ± 5.2 mm Hg; P < .01). During a median follow-up period of 89.1 months, the mean maximum aneurysm diameter became significantly smaller than that observed before the operation (53.23 ± 10.9 mm vs 59.86 ± 11.77 mm). The postoperative maximum aneurysm diameter decreased in 76 patients and was stable in 22 patients. One patient with aneurysm enlargement was transferred to open surgery because of a type IV endoleak, and another patient with no blood flow into the aneurysm sac observed by computed tomography angiography was closely followed up. Four patients received repeated endovascular treatment after the occurrence of type IB endoleak and aneurysm enlargement. After a median follow-up of 89.1 months, the cumulative survival rate was 90.7%, 80.4%, 72.0%, 58.9%, and 51.4% after 1 year, 3 years, 6 years, 8 years, and 10 years after the operation, respectively. There was no recurrent type I endoleak, distal embolization, migration, kinking, or malfunction after FS injections during the perioperative period and follow-up. CONCLUSIONS: FS sac filling combined with intrasac pressure measurement is a simple and effective treatment method to eliminate TIAE after EVAR, especially for patients with challenging proximal neck anatomy. This method could expand the current indications of EVAR.

Endovascular Treatment for Iliofemoral Vein Thrombosis with Composite Stents.

BACKGROUND: To evaluate the applicability of endovascular treatment for iliofemoral vein thrombosis with composite stents. METHODS: Between September 2013 and August 2016, 29 consecutive patients underwent endovascular therapy with composite stents for iliofemoral vein thrombosis and were followed up at our institution. All the patients with acute or chronic iliofemoral vein thrombosis enrolled in this study were evaluated by color Doppler ultrasonography and diagnosed by venography. Treatment measures and related complications were recorded, and cumulative stent patency was assessed with Kaplan-Meier curves. RESULTS: Patients with acute iliofemoral vein thrombosis (n = 7) were successfully treated with catheter-directed thrombolysis treatment, balloon angioplasty, and stents, whereas patients (n =  = 22) with chronic deep vein thrombosis were treated successfully by balloon angioplasty and stent only. Among all patients, 2 stents were inserted in 25 patients, whereas 3 stents were deployed in 4 patients. Endovascular treatment for iliofemoral vein thrombosis with laser-cut stents combined with Wallstents showed primary patency of treated limbs at 6, 12, and 24 months was 96.6%, 93.1% and 93.1%, respectively. Mean duration of follow-up was 23 months, and there was no occurrence of contralateral vein thrombosis during follow-up by ultrasound. CONCLUSIONS: Iliofemoral vein thrombosis was successfully recanalized by endovascular therapy with composite stents, and there was no occurrence of contralateral vein thrombosis by ultrasound during follow-up.

Mzb1 Attenuates Atherosclerotic Plaque Vulnerability in ApoE-/- Mice by Alleviating Apoptosis and Modulating Mitochondrial Function.

In this study, we investigated the protective role of Mzb1 in atherosclerotic plaque vulnerability. To explore the impact of Mzb1, we analyzed Mzb1 expression, assessed apoptosis, and evaluated mitochondrial function in atherosclerosis (AS) mouse models and human vascular smooth muscle cells (HVSMCs). We observed a significant decrease in Mzb1 expression in AS mouse models and ox-LDL-treated HVSMCs. Downregulation of Mzb1 increased ox-LDL-induced apoptosis and cholesterol levels of HVSMCs, while Mzb1 overexpression alleviated these effect. Mzb1 was found to enhance mitochondrial function, as evidenced by restored ATP synthesis, mitochondrial membrane potential, and reduced mtROS production. Moreover, Mzb1 overexpression attenuated atherosclerotic plaque vulnerability in ApoE-/- mice. Our findings suggest that Mzb1 overexpression regulates the AMPK/SIRT1 signaling pathway, leading to the attenuation of atherosclerotic plaque vulnerability. This study provides compelling evidence for the protective effect of Mzb1 on atherosclerotic plaques by alleviating apoptosis and modulating mitochondrial function in ApoE-/- mice.

Suppression of endoplasmic reticulum stress by 4-PBA enhanced atherosclerotic plaque stability via up-regulating CLOCK expression.

Endoplasmic reticulum (ER) stress refers to a condition where the normal functioning of the ER is disrupted due to a variety of cellular stress factors. As a result, there is an accumulation of unfolded and misfolded proteins within the ER. Numerous studies have shown that ER stress can exacerbate inflammatory reactions and contribute to the development of various inflammatory diseases. However, the role of ER stress in the stability of atherosclerotic plaques remains poorly understood. In this study, we aimed to explore the potential impact of a specific ER stress inhibitor known as 4-phenyl butyric acid (4-PBA) on atherosclerosis in mice. The mice were fed a high-fat diet, and treatment with 4-PBA significantly improved the stability of the atherosclerotic plaques. This was evidenced by a reduction in oxidative stress and an increase in circadian locomotor output cycles kaput (CLOCK) protein and mRNA expression within the plaques. Additionally, 4-PBA reduced the expression of ER stress-related proteins and decreased apoptosis in the atherosclerotic plaques. In vitro investigation, we observed the effect of 4-PBA on vascular smooth muscle cells (VSMCs) that were exposed to oxidized low-density lipoprotein (ox-LDL), a significant contributor to the development of atherosclerosis. 4-PBA reduced reactive oxygen species (ROS) production and attenuated apoptosis, GRP78 and CHOP protein expression in ox-LDL-Induced VSMCs via up-regulating CLOCK expression. However, when the short hairpin RNA against CLOCK (sh-CLOCK) was introduced to the VSMCs, the protective effect of 4-PBA was abolished. This suggests that the up-regulation of CLOCK expression is crucial for the beneficial effects of 4-PBA on atherosclerotic plaque stability. This finding suggests that targeting ER stress and modulating CLOCK protein levels might be a promising way to enhance the stability of atherosclerotic plaques.

Comparison of branched, fenestrated, and parallel strategies for endovascular treatment of thoracoabdominal aortic pathologies involving visceral regions.

Purpose: To compare the long-term efficacy of the parallel stent graft (PSG), fenestrated stent graft (FSG), and branched stent graft (BSG) techniques to treat thoracoabdominal aortic pathologies. Materials and methods: In total, 291 patients with thoracic aortic aneurysm (TAA) and dissection (TAD) involving visceral arteries who underwent PSG (n = 85; 15 TAA and 70 TAD), FSG (n = 107; 47 TAD and 60 TAA), or BSG (n = 99; 37 TAD and 62 TAA) were included from multiple centers from January 2015 to December 2022, and a total of 1,108 visceral aortic branches were reconstructed. Results: The average reconstruction time of each visceral aortic branch for FSG, BSG, and PSG is 27.5 ± 12.1, 23.2 ± 11.9, and 18.8 ± 11.8 min, respectively (P < 0.01). The free-from-endoleak rate at the last follow-up for FSG, BSG, and PSG was 86.9%, 91.9%, and 60.0%, respectively. The last follow-up patency rate for FSG, BSG, and PSG was 85.0%, 91.9%, and 94.1%, respectively. The average reconstruction price of each visceral aortic branch for FSG, BSG, and PSG was 41.40 ± 3.22 thousand RMB, 41.84 ± 3.86 thousand RMB, and 42.35 ± 4.52 thousand RMB, respectively (P = 0.24). Conclusion: To treat the aortic pathologies involving the visceral segment, BSG had a lower endoleak rate and higher branch patency rate when compared with the FSG and PSG techniques. The expense of BSG was comparable to the other two techniques.

Circadian gene CLOCK accelerates atherosclerosis by promoting endothelial autophagy.

Atherosclerosis (AS) is a chronic inflammatory disease which gives rise to life-threatening complications like ischemic stroke. Rupture of carotid atherosclerotic plaque is the main cause of ischemic stroke. Emerging evidence has demonstrated that disturbed circadian rhythms could accelerate the progression of atherosclerosis by regulating endothelial function. Moreover, our previous study implicated the circadian gene circadian locomotor output cycles kaput (CLOCK) in the pathogenesis of unstable plaques. In this study, we explored the underlying mechanism that CLOCK mediates endothelial cell autophagy involved in the progression of AS. Circadian and autophagy gene expression was analyzed in the GSE41571 dataset and human carotid atherosclerotic plaque samples. Then we used ox-LDL to treat HUVECs, and analyzed CLOCK and autophagy gene in endothelial cells. Besides that, we comprehensively analyzed in vivo experiments to explore the function of CLOCK in autophagy and atherosclerosis using different staining including HE, MT and IF staining. In the dataset and patient samples, CLOCK expression and autophagy were decreased in the unstable plaque group compared with the stable group. Decreased Beclin1, ATG5, LC3, and CLOCK were also observed in HUVECs under oxidative stress condition which also enhances cell proliferation. In vivo, we also found decreasing level of CLOCK, Beclin1, LC3 and ATG5 in ApoE-/- mice compared with WT mice. Silencing of CLOCK in ApoE-/- mice may further aggravate atherosclerosis including decreased cap thickness and collagens. Our findings implicated that downregulation CLOCK would impair endothelial cell autophagy and accelerate atherosclerotic plaque, which provides a novel strategy for treatment of progression in AS.

Diagnostic Value of Circulating microRNAs for In-Stent Restenosis in Patients with Lower Extremity Arterial Occlusive Disease.

In-stent restenosis (ISR) is still a major cause of failure of endovascular stenting treatment in patients with lower extremity arterial occlusive disease (LEAOD). Sensitive and reliable biomarkers for early diagnosis to predict ISR should be considered. This study was conducted to explore the diagnostic value of microRNA in predicting ISR in patients with LEAOD after endovascular stenting treatment. From March 2014 to July 2016, 208 patients (170 males and 38 females) with LEAOD undergoing interventional treatment were enrolled in this research. Patients were divided into the restenosis and non-restenosis groups according to routine postoperative angiography. Circulating microRNAs expression were detected in 208 participants, including 78 ISR patients, 68 non-ISR patients and 62 healthy volunteers. We selected 6 microRNAs from microarray screening as candidates for further testing via qRT-PCR. A receiver operating characteristic (ROC) curve was generated to assess the diagnostic value of circulating microRNAs in predicting ISR for LEAOD patients. The results showed that circulating microRNA-320a and microRNA-572 in patients with ISR (n = 78) had significantly higher expression levels than it from non-ISR and healthy volunteers. By receiver operating characteristic curve analysis, the sensitivity was 82.1% and the specificity was 63.8% for microRNA-320a; the sensitivity was 69.2% and the specificity was 68.9% for microRNA-572, and the AUC was 0.766 and 0.690 for detection of ISR, respectively. Furthermore, 78 patients with ISR had significantly higher circulating expression levels of microRNA-3937 and microRNA-642a-3p and lower circulating expression levels of microRNA-4669 and microRNA-3138 compared with 68 non-ISR patients and 62 healthy volunteers, but they have no significant difference. We found that differential circulating microRNA expression in patients after stenting with ISR, and the data indicate that circulating microRNA-320a and microRNA-572 have promising value in diagnosing ISR in patients with LEAOD.

Risk factors of distal segment aortic enlargement after complicated type B aortic dissection.

OBJECTIVES: Distal segment aortic enlargement (DSAE) is a common complication that influences the long-term prognosis of type B aortic dissection (TBAD) after thoracic endovascular aortic repair (TEVAR). In this study, a multivariate analysis was performed to find potential factors predictive of DSAE. METHODS: A single-center retrospective study was performed from 1999 to 2016. Included in the study were complicated TBAD patients who underwent TEVAR with uncovered residual tears. Based on the diameter of the distal segment of the uncovered aorta, we assigned patients to an enlargement group and a non-enlargement group. Data extracted from the medical records included demographic and clinical characteristics and follow-up computed tomography angiography data. The primary endpoints were the all-cause mortality and the presumably aortic-related events that required reintervention during the follow-up period. RESULTS: For the 333 patients, all-cause mortality was 38 (11.41%), and 76 (22.82%) patients underwent reintervention. A total of 70 (21.02%) patients experienced DSAE, among them were 2 patients who died of aortic rupture and 58 patients who accepted reintervention. Multivariate analysis reviewed independent risk factors of postoperative DSAE, including current smoking, the residual length of the patent false lumen, the postoperative number of dissection tears in the thoracic aorta and type III aortic arch; as well as protective factors, including the application of a restrictive bare stent (RBS), the length of covered stent in the descending thoracic aorta, and the distance from the residual first tear to the left subclavian artery (LSA). CONCLUSION: DSAE after TEVAR for patients with a complicated TBAD can be influenced by their current smoking habit, the residual length of patent false lumen, the postoperative number of dissection tears in the thoracic aorta and the aortic arch type. Meanwhile, RBS usage, the length of the covered stent in the descending thoracic aorta and the distance from the residual first tear to the LSA could have positive effect on the prognosis.

A Promising Treatment of Distal Entry Tears Located in Branched Area of Abdominal Aorta With Coil-Stent Tear Occlusion Device: an Animal Experiment.

This study aims to evaluate the effect of coil-stent tear occlusion device in treating entry tears located in branched area of abdominal aorta. An abdominal aortic dissection animal model was constructed by mesh suturing method. The animal models were treated by the occlusion device and were evaluated by computed tomography angiography (CTA) 1 month later. Eighteen pigs were adopted in the abdominal aortic dissection modeling experiment, two of them died of cardiopulmonary arrest during the operation. Sixteen models survived, two of them were found complete false lumen thrombosis by CTA 3 days after the operation. The false lumen kept patency in the remaining 14 cases which were then implanted with the occlusion device. The procedure was successful in 13 cases except for one. The coil-stent tear occlusion device provides a novel method for tears located in the branched area of abdominal aorta, and is worth of further study.

In Vivo Detection and Measurement of Aortic Aneurysm and Dissection in Mouse Models Using Microcomputed Tomography with Contrast Agent.

Objectives: The aim of this study was to evaluate the potential of microcomputed tomography (micro-CT) using the intravascular contrast agent ExiTron nano 12000 for aorta imaging and monitoring the dynamic changing process of the aorta in mouse models with aortic aneurysm and dissection. Materials and Methods: Experiments were performed on healthy mice and mice with aortic dissection. Mice that were developing aortic dissection and healthy mice underwent micro-CT imaging after injection of ExiTron nano 12000. Time-dependent signal enhancement (at 1, 2, 3, 6, and 12 hours after intravenous injection of the contrast agent, respectively) in the aorta of healthy mice was measured to confirm the optimal imaging time of aorta. Various contrast agent doses (70, 100, and 150 µl per 25 g mouse, respectively) were investigated to determine the optimal required dose for imaging of the aorta. The mice were scanned with micro-CT at 1, 14, and 28 days after onset of aneurysm and dissection to monitor the dynamic changing process of the aorta. Mouse aortas were stained with hematoxylin and eosin staining, and the diameter of the aorta was measured and compared with those obtained by micro-CT. Results: Time-dependent signal enhancement in the aorta shows that the contrast agent has a long blood half-life of 6 hours, with a peak enhancement at 2 hours after injection. Injection of 100 µl ExiTron nano 12000 per 25 g mouse allows for effective visualization of the aorta. Micro-CT combined with contrast agent can monitor the changing process of the aorta in the mouse model of aortic aneurysm and dissection dynamically. The values of the diameter of the aortas obtained from the in vivo micro-CT imaging were compared with those obtained from histology and showed a significant correlation (R 2 = 0.96). Conclusions: These data demonstrate that in vivo micro-CT is an accurate and feasible technique to detect aortic aneurysm or dissection in a mouse model, and the micro-CT technique using the innovative contrast agent ExiTron nano 12000 allows for monitoring various processes dynamically such as aortic remodeling in longitudinal studies.

Local upregulation of interleukin-1 beta in aortic dissecting aneurysm: correlation with matrix metalloproteinase-2, 9 expression and biomechanical decrease.

OBJECTIVES: Our goal was to examine whether interleukin-1 beta (IL-1ß) originates locally and its possible relationship with matrix metalloproteinases (MMPs), apoptosis, elastin fibres and biomechanics in aortic dissecting aneurysms (DAs). METHODS: Aortic DAs were induced in 24 rats with ß-aminopropionitrile (BAPN); another 12 rats without BAPN were designated as controls. Then IL-1ß levels were measured both in the circulation and in local aortic specimens. The expression of MMP-2 and MMP-9 and Victoria blue and TUNEL staining were also detected. Biomechanical parameters such as the elasticity modulus were used to detect the biomechanical changes in the aortic wall. The correlation of IL-1ß, MMP-2, MMP-9, apoptosis and biomechanical properties was analysed. RESULTS: Seventeen rats (17/24, 71%) in the BAPN-treated group died of DA rupture. IL-1ß levels were dramatically increased in the DA specimens but not in the circulation. Victoria blue staining confirmed the formation of the DA and the reduction of elastin content after induction by BAPN. The extent of apoptosis in the aortic media was dramatically higher in rats with BAPN-induced DA than that in the control group and that in rats treated with BAPN but without DA. MMP-2 and MMP-9 levels were significantly increased in BAPN-treated rats compared to the controls, but no statistical significance was found between rats with and without DA. There were significant differences in biomechanical parameters, such as the elasticity modulus. Among the 3 groups, IL-1ß was positively correlated with MMP-2 and MMP-9 levels and with the elasticity modulus but not with apoptosis. CONCLUSIONS: Local IL-1ß might participate in the formation of aortic DA through the upregulation of MMP-2 and MMP-9 and the breakage of elastin fibres, which finally weakens the biomechanical properties of the aortic wall.

Antiplatelet and anticoagulant for prevention of reocclusion in patients with atrial fibrillation undergoing endovascular treatment for low extremity ischemia.

BACKGROUND: The purpose of this study is to report the efficacy of the mono antiplatelet plus anticoagulation therapy for prevention of reocclusion in patients with atrial fibrillation (AF) undergoing endovascular treatment for lower extremity ischemia. METHODS: From March 2014 to July 2016, 32 (21 males; range, 68-84 years) patients were submitted to endovascular therapy for low extremity ischemia with AF and all were treated with endovascular treatments to correct underlying lesions. Then 20 patients receive aspirin plus rivaroxaban post-operation and 12 patients receive aspirin plus warfarin to prevent reocclusion. RESULTS: Complete reconstruction of occluded femopopliteal arteries with unimpeded blood flow to legs were successfully obtained in all 32 patients; 12 (37.5%) patients had acute ischemia, 17 (53.1%) patients had chronic ischemia, 3 (9.4%) patients had acute on chronic ischemia. Endovascular treatments including percutaneous transluminal angioplasty (PTA) and stenting were performed to correct residual lesions after the thrombolytic/thrombectomy procedure or to correct native lesions for chronic patients. All 32 patients showed significant improvements in symptoms and 4 patients improved completely. The mean ankle-brachial index (ABI) had risen from 0.43±0.21 preoperatively to 0.81±0.16 postoperatively (P<0.01), and the primary patency rates were 88.9% at 12 months, and 81.5% at 24 months. No episodes of major bleeding and only one patient showed positive fecal occult blood tests during the follow-up. CONCLUSIONS: The mono antiplatelet plus anticoagulation therapy offers a safe and effective alternative for prevention of reocclusion in patients with AF undergoing endovascular treatment for lower extremity ischemic.