Costunolide mitigates inflammation and promotes extracellualr matrix integrity of thoracic aortic dissection by inhibiting NF-κB signaling.

BACKGROUND: Thoracic aortic dissection (TAD) is one of the most fatal cardiovascular diseases. One of its important pathological characteristics is the local inflammatory response. Many studies have found that Macrophage polarization plays an extremely critical role in the inflammatory progression and tissue remodeling of TAD. Costunolide (CTD) has an improving effect on oxidative stress and inflammation in the body. However, whether it can promote the integrity of extracellular matrix in Aortic dissection and its mechanism are still unclear. METHODS: The male C57BL/6J mice were used to construct an animal model of TAD with ß-aminopropionitrile (BAPN) (100 mg/kg/day, lasting for 28 days), and then CTD (10 mg/kg or 100 mg/kg) was injected intraperitoneally for 28 days to check the survival rate, TAD incidence, aortic morphology and other indicators of the mice. Using hematoxylin-eosin (HE), Masson, Elastin van Gieson (EVG) staining, immunofluorescence (IF), and immunohistochemical staining, the study aimed to determine the therapeutic effects of CTD on an animal model with BAPN-induced TAD. To enhance the examination of the regulatory mechanism of CTD, we conducted transcriptome sequencing on arterial tissues of mice in both the BAPN group and the BAPN + CTD100 group. Next, ANG II were used to construct TAD model in vascular smooth muscle cells (VMSCs). The effects of CTD on the proliferation, migration, invasion, and apoptosis of ANG II-induced cells are to be detected. The expression of MMP2, MMP9, P65, and p-P65 in each group will be examined using Western blot. Finally, the overexpression of IκB kinaseß (IKKß) will be established in VMSCs cells to further explore the protective function of CTD. RESULTS: The result showed that CTD significantly inhibited BAPN induced mortality and TAD incidence in the animal model, improved aortic vascular morphology, promoted the integrity of extracellular matrix in TAD, reduced tissue inflammation, reduced the accumulation of M1 macrophage, promoted M2 macrophage polarization, and reduced the expression of NF-κB pathway related proteins. Mechanistically, CTD significantly weakened the proliferation, migration, invasion, and apoptosis. p-P65 protein expression of TAD cells were induced by ANG II and IKK-ß. CONCLUSION: CTD has the potential to alleviate inflammation, VSMC apoptosis, MMP2/9 levels, and enhance extracellular matrix integrity in TAD by inhibiting the NF-κB signaling pathway.

One month follow-up of carotid endarterectomy with in-hospital preoperative aspirin monotherapy and postoperative dual antiplatelet therapy in asymptomatic and symptomatic patients: A multi-center study.

Background: There is currently no consensus regarding the optimal perioperative antiplatelet strategy for carotid artery surgery. This multicentre study aimed to analyse the association between preoperative aspirin monotherapy following postoperative dual antiplatelet therapy (DAPT) and the risk for stroke and death after carotid endarterectomy (CEA). Methods: This cohort study included 821 patients with carotid artery stenosis who underwent CEA. Primary outcomes included any stroke or death up to the one-month postoperative follow-up. Multilevel multivariate regression analyses and descriptive statistics were performed. Results: Patients were predominantly male (53 %), with a mean age of 66.2 years. The primary outcome occurred in 1.6 % of patients. Univariate and multivariate analyses revealed that patients with chronic obstructive pulmonary disease (COPD) exhibited a high risk for stroke or death (P = 0.011). The occurrence of any local complications in the neck was accompanied by an increase in diastolic blood pressure (DBP) (P = 0.007). Patients with a high systolic blood pressure (SBP) (P = 0.002) experienced a longer operative duration. The length of hospital stay was longer in the patients with COPD (P = 0.020), minor stroke (P = 0.011), and major stroke (P = 0.001). A positive linear correlation was found between SBP and operative duration in the overall population (ß 0.4 [95 % confidence interval (CI) 0.1-0.7]; P = 0.002). The resultant curve for DBP and any local complications in the neck exhibited a two-stage change and one breakpoint in the entire population (k = 68 mmHg, <68; odds ratio [OR] 0.9 [95 % CI 0.7-1.1], P = 0.461; ≥68: OR 1.1 [95 % CI 1.0-1.1], P = 0.003). Conclusions: Preoperative aspirin monotherapy and postoperative DAPT were safe and effective antiplatelet treatments for patients who underwent CEA.

Retrospective, multicenter study of surgical treatment for carotid body tumors with or without preoperative embolization.

Background: Carotid body tumor (CBT) is the most common head and neck paraganglioma. Whether preoperative embolization benefits CBT patients who will receive surgical resection is still controversial. Methods: In this multi-center retrospective study, we collected data from patients with CBT who received surgical treatment without (group A) or with preoperative embolization (group B) from 2011 to 2019. The primary outcome was the rate of death or stroke after 3 years of follow-up. The secondary outcomes of the study were length of operation (LOO), intraoperative blood loss (IBL), length of stay (LOS), rate of recurrence, and rate of cranial nerve (CN) injuries. Descriptive statistics were used to analyze the demographics, clinical characteristics, complications, and follow-up results of the patients. Results: Between January 2011 and October 2019, 261 consecutive patients (107 male and 154 female) entered analysis. After 3 years of follow-up, no patient died in both groups. Only three patients with stroke were detected: 2/226 (0.9%) in group A vs. 1/35 (2.9%) in group B (p = .308). The LOO in group A was 132.6 ± 64.6 min compared with 152.9 ± 40.4 min in group B (p = .072). IBL in group A was 375.4 ± 497.8 ml compared with 448.0 ± 270.8 ml in group B (p = .400). LOS in group A was 8.3 ± 2.0 days compared with 7.4 ± 1.7 days in group B (p = .016). Seventy-two CN injuries were detected: 65/226 (28.8%) in group A vs. 7/35 (20.0%) in group B (p = .281). There were 65 temporary CN injuries (59 in group A vs. 6 in group B) (p = .254) and seven permanent CN injuries (6 in group A vs. 1 in group B) (p = .945). Three most frequently injured cranial nerves were the pharyngeal branch and superior laryngeal nerve (12.3%), recurrent laryngeal nerve (7.7%) and vagus nerve (7.3%). Conclusion: There was insufficient evidence to support the efficacy of preoperative embolization. CBT resection alone had a similar rate of stoke, recurrence, and CN injuries when compared with CBT resection with preoperative arterial embolization. Meanwhile, CBT resection alone did not increase LOO and IBL.

Extracellular traps and the role in thrombosis.

Thrombotic complications pose serious health risks worldwide. A significant change in our understanding of the pathophysiology of thrombosis has occurred since the discovery of extracellular traps (ETs) and their prothrombotic properties. As a result of immune cells decondensing chromatin into extracellular fibers, ETs promote thrombus formation by acting as a scaffold that activates platelets and coagulates them. The involvement of ETs in thrombosis has been reported in various thrombotic conditions including deep vein thrombosis (DVT), pulmonary emboli, acute myocardial infarction, aucte ischemic stroke, and abdominal aortic aneurysms. This review summarizes the existing evidence of ETs in human and animal model thrombi. The authors described studies showing the existence of ETs in venous or arterial thrombi. In addition, we studied potential novel therapeutic opportunities related to the resolution or prevention of thrombosis by targeting ETs.

Low red blood cell predicts high risk of temporary postoperative complications after carotid body tumor surgical resection.

Background: Carotid body tumor (CBT) is a rare paraganglioma located at the carotid bifurcation. The red blood cell count, hemoglobin, and hematocrit are indexes to be evaluated in blood routine tests. The purpose of this study was to clarify their predictive value for temporary postoperative complications in patients that had undergone CBT surgery. Methods: This retrospective trial included data from 169 patients received surgical treatment for CBT from October 2008 to September 2018 in this retrospective study. Postoperative follow-up was conducted under the guidance of both vascular surgeon and neurologist. The symptoms existed less than 2 years postoperatively were regarded as temporary injuries. The red blood cell count, hemoglobin, and hematocrit were obtained from the complete blood count results of the participants. Analyses of multilevel multivariable regression and descriptive statistics were conducted. Results: The baseline data showed no significant difference. Patients were predominantly women (53.8%), with a mean age of 42.6 years. The total incidence of temporary postoperative complications was 22 (13.0%), including transient ischemic attack (8, 4.7%), tongue bias (7, 4.1%), dysphagia (2, 1.2%), hoarseness (4, 1.8%), and eyelid ptosis (1, 2.4%). The univariate and multivariate regression analysis results revealed that the occurrence of temporary postoperative complications was increased with age [odd ratio (OR, 0.09; 95% CI (CI), 0.9-1.0; P = 0.014], length of operation time (OR, 1.0; 95% CI, 1.0-1.0; P = 0.005), Shamblin type II vs. I (OR, 0.1; 95% CI, 0.0-0.5; P = 0.008), red blood cell count postoperative (OR, 0.2; 95% CI, 0.1-0.8; P = 0.026), hemoglobin (OR, 0.9; 95% CI, 0.9-1.0; P = 0.011), and hematocrit (OR, 0.8; 95% CI, 0.7-1.0; P = 0.025). The smooth curve fitting showed that the trend of complications occurrence rate was reduced with the increase of patients' postoperative red blood cell count, hemoglobin, and hematocrit. Gender, weight, length of operation, Shamblin type, postoperative red blood cell count, hemoglobin, and hematocrit were included in the risk model with AUC = 0.86. Conclusion: These patients with CBT who received surgical resection with low postoperative red blood cell, hemoglobin, or hematocrit had a high risk of temporary postoperative complications. The risk prediction model established for predicting temporary postoperative complications showed satisfactory prediction effects.

BMAL1 modulates smooth muscle cells phenotypic switch towards fibroblast-like cells and stabilizes atherosclerotic plaques by upregulating YAP1.

BACKGROUND: Ischemic heart diseases and ischemic stroke are closely related to circadian clock and unstable atherosclerotic plaques. Vascular smooth muscle cells (VSMCs) can stabilize or destabilize an atherosclerotic lesion through phenotypic switch. BMAL1 is not only an indispensable core component in circadian clock but also an important regulator in atherosclerosis and VSMCs proliferation. However, little is known about the modulation mechanisms of BMAL1 in VSMCs phenotypic switch and atherosclerotic plaque stability. METHODS: We integrated histological analysis of human plaques, in vivo experiments of VSMC-specific Bmal1-/- mice, in vitro experiments, and gene set enrichment analysis (GSEA) of public datasets of human plaques to explore the function of BMAL1 in VSMCs phonotypic switch and plaque stability. FINDINGS: Comparing to human unstable plaques, BMAL1 was higher in stable plaques, accompanied by elevated YAP1 and fibroblast maker FSP1 which were positively correlated with BMAL1. In response to Methyl-ß-cyclodextrin-cholesterol, oxidized-low-density-lipoprotein and platelet-derived-growth-factor-BB, VSMCs embarked on phenotypic switch and upregulated BMAL, YAP1 and FSP1. Besides, BMAL1 overexpression promoted VSMCs phonotypic switch towards fibroblast-like cells by transcriptionally upregulating the expression of YAP1. BMAL1 or YAP1 knock-down inhibited VSMCs phonotypic switch and downregulated FSP1. Furthermore, VSMC-specific Bmal1-/- mice exhibited VSMCs with lower YAP1 and FSP1 levels, and more vulnerable plaques with less collagen content. In addition, BMAL1 suppressed the migration of VSMCs. The GSEA results of public datasets were consistent with our laboratory findings. INTERPRETATION: Our results highlight the importance of BMAL1 as a major regulator in VSMCs phenotypic switch towards fibroblast-like cells which stabilize an atherosclerotic plaque.

Reverse "cheese wire" fenestration for abdominal aortic dissection repair: a case report and literature review.

BACKGROUND: Aortic dissection is one of the most common emergency condition leading to internal organs or lower limb ischemia and aortic rupture. Herein, we described a reverse "cheese wire" endovascular fenestration repair (CWFER) in a patient with complicated abdominal aortic dissection which had never been reported. CASE PRESENTATION: A 62-year-old male presented abdominal tear-like pain and acute ischemia of the right lower extremity during the endovascular treatment of celiac trunk aneurysms. Computed tomography angiography (CTA) and digital subtraction angiography (DSA) showed abdominal aortic type B dissection with acute ischemia of the right lower extremity preoperatively. After a detailed preoperative examination, the patient then was performed a reverse CWFER. So far, the patient has been followed-up for 6 months, postoperative CTA demonstrated good stent-graft expansion and perfusion of bilateral common iliac arteries; also, no endoleak was detected. CONCLUSIONS: The right iliac artery in this patient supplied by false lumen, which lead to acute ischemia of the right lower extremity, needed to be treated as an emergency and dealt with promptly. CWFER is a very high-risk treatment that requires the rich experience of vascular surgeon and accurate assessment of aortic dissection. After interventional treatment, the patient recovered uneventfully after 6 months' follow-up.

A Retrospective Study Comparing the Effectiveness and Safety of EXOSEAL Vascular Closure Device to Manual Compression in Patients Undergoing Percutaneous Transbrachial Procedures.

BACKGROUND: This study aimed to assess the safety and efficacy of EXOSEAL vascular closure device (EVCD) insertion by comparing its performance with manual compression (MC) in achieving hemostasis at the brachial artery puncture site. METHODS: A retrospective study of brachial artery access by using either MC or EVCD for achieving hemostasis from March 2016 to October 2017 was conducted. Patients with Stanford type B aortic dissection (TBAD) undergoing percutaneous transbrachial procedures were included. Time to hemostasis (TTH) was the primary efficacy end point. Seven-day incidence of major access site-related complications was the primary safety end point. TTH and major and minor complications associated with treatment of these 2 groups were also evaluated. RESULTS: A total of 157 patients with TBAD undergoing percutaneous transbrachial procedures entered the analysis. Of these, 107 patients underwent EVCD insertion and 50 patients underwent MC. The baseline characteristics of the 2 groups were similar. TTH was significantly shorter for EVCD over MC (P < 0.05). The TTH ≥10 min in the MC group was 100.0% (n = 50), but in the EVCD group, it was ≤2 min, 87.9% (n = 107); 2-5 min, 7.5% (n = 107); and ≥10 min, 4.7% (n = 107). The EVCD group had several major complications, while the MC group had none. Two patients (1.9%, n = 107) required vascular repair, one patient (0.6%, n = 107) required blood transfusion, and 1 patient (0.6%, n = 107) developed upper limb numbness and weakness after EVCD deployment. Minor complication such as the occurrence of hematoma (≤5 cm) in the MC group was 4 (8.0%) but was also 4 (3.7%) in the EVCD group, showing statistically significant difference (P = 0.030). The incidence of ecchymosis was 8 (7.5%) in the EVCD group when compared with 13 (26.0%) in the MC group, which showed statistically significant difference (P = 0.001). Other major and minor complications showed no significant differences between these 2 groups. CONCLUSIONS: After invasive procedures by 6F percutaneous access via the brachial artery in preprocedurally fully anticoagulated patients, TTH was significantly reduced in patients who underwent EVCD when compared with patients who underwent MC. MC is a safer and more convenient way to achieve hemostasis but has higher incidence of minor complications.

Outcome of Surgical Treatment for Carotid Body Tumors in Different Shambling Type Without Preoperative Embolization: A Single-Center Retrospective Study.

BACKGROUND: Carotid body tumor (CBT) is the most common head and neck paragangliomas. Surgical resection is the golden standard management for CBT. While preoperative embolization is still controversial, long-term outcomes and perioperative results are still deficient. We, here, presented the outcomes of surgical treatment for CBT without preoperative embolization at our institution. METHODS: In this retrospective study, we collected data from 101 patients who received surgical treatment for CBTs without preoperative embolization from 2011 to 2016. In addition, we attempted to conduct 2 years of follow-up under the guidance of both neurologist and vascular surgeon. Patients' demographics, clinical characteristics, complications, and follow-up results were all analyzed with descriptive statistics. RESULTS: Complete resection of the CBT was achieved in 101 cases (100%). Postoperative adverse events (AEs) mostly observed during hospitalization were as follows: tongue bias (I: 4, 36.4%; II: 8, 19.5%; III: 13, 26.5%), hoarseness (I: 1, 9.1%; II: 4, 9.8%; III: 7, 14.3%), dysphagia (I: 0; II: 2, 4.9%; III: 7, 14.3%), and hematoma (I: 0; II: 0; III: 1, 2.0%). No other serious AEs were observed. The total incidence of AEs in type I patients was 5 (45.5%), 14 (34.1%) in type II, and 28 (57.1%) in type III, and the type III group has significantly higher than the other two groups. At the end of 2 years of follow-up, there were no AEs in type I patients. The number of patients with AEs in type III was greater than that in type II, although there was no significant difference. Based on our findings, 3 most commonly injured cranial nerves (CNs) after surgical resection of CBT were CN XII (hypoglossal nerve, 21.9%), CN X (vagus nerve, 20.3%), and recurrent laryngeal nerve (18.8%). CONCLUSIONS: Surgical management without preoperative embolization for CBT patients is a safe and effective therapeutic approach.

miR-27a regulates vascular remodeling by targeting endothelial cells' apoptosis and interaction with vascular smooth muscle cells in aortic dissection.

Rationale: Aortic dissection (AD) is caused by functional disorder of cells in the aortic wall, which is largely attributed to vascular remodeling. Therapeutic strategies for AD remain limited due to our incomplete understanding of the role of endothelial cells (ECs) in AD pathogenesis. This study aimed to identify the regulatory role of miR-27a in AD and provide a mechanistic basis for a non-invasive treatment of AD. Methods: We harvested aortas from normal and AD patients to explore the expression of miR-27a. In vitro and in vivo assays were preformed to explore the biological effects of differential expression of miR-27a in ECs and its regulatory effect on AD. Results: MiR-27a was lower in intima of AD samples than in healthy individuals. Downregulation of miR-27a in EC was due to up-regulated expression of fas-associated protein with death domain (FADD) and the activation of apoptosis pathway, which led to apoptosis of ECs. Migration of vascular smooth muscle cells was promoted by EC after downregulation of miR-27a due to enhancement of growth/differentiation factor 8 (GDF8) and repression of matrix metalloproteinase-20 (MMP20) in the co-culture system supernatants. Increase in FADD and apoptosis of ECs to induce AD was shown using mouse models of AD in which miR-27a was stably knocked-down by antagomir. Up-regulation of miR-27a by agomir led to a protective effect on AD. Conclusion: Treatment with miR-27a activator that targets apoptosis of ECs strongly diminished occurrence of AD, providing a new strategy for this disease.

Upregulation of miR-330-5p is associated with carotid plaque's stability by targeting Talin-1 in symptomatic carotid stenosis patients.

BACKGROUND: The aim of this study was to investigate the relationship between Talin-1 and stability of carotid atherosclerosis plaque and also find out the role of miRNA, as an upstream regulator, in regulating the expression level of Talin-1. METHODS: Human carotid plaques were obtained from 20 symptomatic carotid stenosis patients who underwent carotid endarterectomy (CEA) in our hospital between October 2014 and August 2017. Western blot analysis and immunohistochemistry was carried out to detect the distribution and expression level of Talin-1 in each plaque sample. The content of miRNAs in carotid plaque was decected by quantitative reverse transcription polymerase chain reaction (RT-qPCR), and the relative expression levels were calculated by 2-△△Ct method after the (cycle threshold) Ct value (power amplification knee point) was obtained. Dual-luciferase reporter assays were applied to verify the successful transfections. Finally, we compared all the groups with independent-samples t-test and one-way analysis of variance (ANOVA). RESULTS: Talin-1 was significantly downregulated in human unstable carotid plaque samples compared with stable carotid plaques (P < 0.05), and the distribution of Talin-1 was mainly found in the fibrous cap of carotid plaque. The overexpression of miRNA-330-5p was found in unstable carotid plaque, which significantly induced the inhibition of expression level of Talin-1. CONCLUSION: Upregulated miR-330-5p may lead to unstable carotid plaques by targeting Talin-1 in symptomatic carotid stenosis patients. This might be a new target for the treatment of atherosclerotic diseases through future studies.

Relationship between serum cortisol level and degree of false lumen thrombosis in patients with uncomplicated type B aortic dissection.

Partial thrombosis of the false lumen in uncomplicated type B aortic dissection (uTBAD) is associated with an increased late mortality risk. Whether the serum cortisol level can affect false lumen thrombosis in patients with uTBAD has not been well characterized. This study was performed on 87 patients with uTBAD. A curve-fitting method was used to analyze the relationship between serum cortisol and partial thrombosis of false lumen. Univariate and multivariate logistic regression analyses were used to identify false lumen partial thrombosis-associated serum cortisol. Curve-fitting's result revealed a characteristic U shape, and 14.0 µg/dL was considered as the cutoff point for serum cortisol. The results of univariate and multivariate logistic regression analyses suggested that when trisecting the serum cortisol level into three parts, the low and high levels of serum cortisol could significantly affect the occurrence of false lumen partial thrombosis compared with the middle level. The odds ratio value of the low and high levels of serum cortisol was 6.12 and 4.65, respectively, in the univariate analysis, and 24.32 and 3.93, respectively, in the multivariate analysis. Low or high levels of serum cortisol might influence the natural result of uTBAD through affecting the false lumen thrombosis.