Association between premature vascular smooth muscle cells senescence and vascular inflammation in Takayasu's arteritis.

OBJECTIVES: Arterial wall inflammation and remodelling are the characteristic features of Takayasu's arteritis (TAK). It has been proposed that vascular smooth muscle cells (VSMCs) are the main targeted cells of inflammatory damage and participate in arterial remodelling in TAK. Whether VSMCs are actively involved in arterial wall inflammation has not been elucidated. Studies have shown that cellular senescence in tissue is closely related to local inflammation persistence. We aimed to investigate whether VSMCs senescence contributes to vascular inflammation and the prosenescent factors in TAK. METHODS: VSMCs senescence and senescence-associated secretory phenotype were detected by histological examination, bulk RNA-Seq and single-cell RNA-seq conducted on vascular surgery samples of TAK patients. The key prosenescent factors and the downstream signalling pathway were investigated in a series of in vitro and ex vivo experiments. RESULTS: Histological findings, primary cell culture and transcriptomic analyses demonstrated that VSMCs of TAK patients had the features of premature senescence and contributed substantially to vascular inflammation by upregulating the expression of senescence-associated inflammatory cytokines. IL-6 was found to be the critical cytokine that drove VSMCs senescence and senescence-associated mitochondrial dysfunction in TAK. Mechanistically, IL-6-induced non-canonical mitochondrial localisation of phosphorylated STAT3 (Tyr705) prevented mitofusin 2 (MFN2) from proteasomal degradation, and subsequently promoted senescence-associated mitochondrial dysfunction and VSMCs senescence. Mitochondrial STAT3 or MFN2 inhibition ameliorated VSMCs senescence in ex vivo cultured arteries of TAK patients. CONCLUSIONS: VSMCs present features of cellular senescence and are actively involved in vascular inflammation in TAK. Vascular IL-6-mitochondrial STAT3-MFN2 signalling is an important driver of VSMCs senescence.

Upregulation of girdin delays endothelial cell apoptosis via promoting engulfment of platelets.

BACKGROUND: Endothelial cells are crucial in maintaining the homeostasis of the blood-brain barrier. Girders of actin filament (Girdin) and phosphor (p)-Girdin are essential for the engulfment of human brain microvascular endothelial cells (HBMECs) into platelets (PLTs), but the potential mechanism remains unclear and requires further study. METHODS: Following PLT and cytochalasin D treatment, Hoechst 33,342 detected apoptosis. The transfection efficiency of the short hairpin RNA targeting Girdin (sh-Girdin) or overexpressing Girdin (OE-Girdin) was determined using western blotting. Sh-Girdin, OE-Girdin, mutated Girdin (m-Girdin), and microfilament binding region deleted Girdin (Del-Girdin) were transfected into HBMECs under PLT conditions. Subsequently, the engulfment of HBMECs by PLTs was detected by flow cytometry and transmission electron microscopy. Girdin and phosphorylated (p)-Girdin levels were quantified by western blot. The positive expression of Girdin was measured by immunohistochemistry (IHC). The localization of PLT, Girdin, and p-Girdin and the engulfment of HBMECs in PLTs were analyzed by confocal microscopy. RESULT: Cytochalasin D overturned the inhibitory effect of PLT on cell apoptosis. OE-Girdin enhanced the fluorescent intensity of PLT-labelling and the engulfment of HBMECs by PLTs, while sh-Girdin, m-Girdin, and Del-Girdin ran reversely. OE-Girdin elevated the Girdin and p-Girdin levels, while sh-Girdin and Del-Girdin were the opposite, but m-Girdin did not affect the p-Girdin and Girdin levels. CONCLUSION: Girdin and p-Girdin were co-located with PLTs in HBMECs. The over-expression of Girdin was identified as being associated with the increasing engulfment of PTLs. Girdin may be an effective target to alleviate endothelial cell apoptosis.

H2O2-responsive VEGF/NGF gene co-delivery nano-system achieves stable vascularization in ischemic hindlimbs.

Peripheral vascular disease (PVD) is a common clinical manifestation of atherosclerosis. Vascular endothelial growth factor (VEGF) gene therapy is a promising approach for PVD treatment. However, due to single-gene therapy limitations and high H2O2 pathological microenvironment, VEGF gene therapy are not as expectations and its clinical application are limited. Synergistic effects of Nerve factors and vascular factors in angiogenesis have attracted attention in recent years. In this study, VEGF and nerve growth factor (NGF) genes co-delivery nanoparticles (VEGF/NGF-NPs) were prepared by using H2O2 responsive 6s-PLGA-Po-PEG as a carrier. 6s-PLGA-Po-PEG could react with H2O2 specifically due to the internal peroxalate bond. Angiogenic effects of VEGF/NGF-NPs has been evaluated in cells and hindlimb ischemia mice model. Results showed that VEGF/NGF-NPs promoted VEGF and NGF co-expression simultaneously, eliminated excessive H2O2, strengthened reactions between SH-SY5Ys and HUVECs, and finally enhanced migration, tube formation, proliferation and H2O2 damage resistance of HUVECs. VEGF/NGF-NPs also recovered blood perfusion, promoted the expression of VEGF, NGF, eNOS and NO, and enhanced vascular coverage of pericytes. Treatment effects of VEGF/NGF-NPs may related to VEGF/eNOS/NO pathway. Altogether, VEGF/NGF-NPs eliminated excessive H2O2 while achieving gene co-delivery, and promoted stable angiogenesis. It's a promising way for PVD treatment by using VEGF/NGF-NPs.

Retrograde Recanalization for Proximal Occlusion of the Right Renal Artery through a Compensated Collateral Artery in a 10-year-old Patient.

BACKGROUND: To describe a retrograde recanalization for the proximal occluded lesion in right renal artery (RRA) in young patient with fibromuscular dysplasia (FMD). METHODS: A 10-year-old girl presented to our hospital with proximal RRA occlusion and refractory hypertension though she took anti-hypertension medicines. Her renin and aldosterone were beyond the normal level in both base state and excited state. Her glomerular filtration rate at right kidney was only 18.4 ml/min. Angiography revealed proximal RRA occlusion and a compensated collateral artery (CCA) from the infrarenal aorta to the RRA. She was thus diagnosed with focal FMD. A retrograde recanalization was performed through this CCA. RESULTS: Angioplasty and stenting were successfully performed to treat the proximal RRA occlusion. Postoperatively, the glomerular filtration rate in the right kidney improved. One-year follow-up revealed that, the blood pressure maintained at normal range without any antihypertensive agents. No other discomfort was complained. CONCLUSIONS: It is feasible to establish a working pathway with patient's compensated collateral artery to treat the renal artery occlusion.

Total Aortic and Branches Repair with Hybrid Therapy in the setting of Marfan Syndrome: A Case Report.

OBJECTIVE: Currently, no standard treatment has been established for the total lesion in patient with Marfan Syndrome (MFS). This case report aims to present a total aortic and branches repair with hybrid therapy in a young patient with MFS. METHODS: Clinical data including imaging manifestation, surgical document, and follow-up results were retrospectively collected and presented. RESULTS: A young patient with MFS underwent multi-stage endovascular aortic management and open surgical repair. On-the-table fenestration technique was applied to reconstruct the branches of the abdominal aorta. A bypass from superior mesenteric artery to celiac trunk was performed. A Bentall operation was conducted to repair his ascending aorta and aortic valves. Finally, in situ fenestration technique was adopted to recanalize the branches of aortic arch. The 18 month follow-up computed tomography angiography demonstrated patency of all the aorta branches. CONCLUSION: It may be feasible to perform the total aortic and branches repair with hybrid therapy in patients with MFS.

Anesthetic choice during transcarotid artery revascularization and carotid endarterectomy affects the risk of myocardial infarction.

OBJECTIVE: Previous studies have shown no differences in the outcomes of transcarotid artery revascularization (TCAR) performed with general anesthesia (GA) vs local or regional anesthesia (LRA). To date, no study has specifically compared the outcomes of TCAR to those of carotid endarterectomy (CEA) stratified by anesthetic type. The aim of the present study was to identify the effect of the anesthetic type on the outcomes of TCAR vs CEA. METHODS: Patients undergoing CEA and TCAR for carotid artery stenosis from 2016 to 2019 in the Vascular Quality Initiative were included. We excluded patients who had undergone concomitant procedures, patients with more than two stented lesions, and patients who had undergone the procedure for a nonatherosclerotic indication. Propensity score matching was performed between the two procedures stratified by the anesthetic type for age, sex, race, presenting symptoms, major comorbidities (ie, hypertension, diabetes, coronary artery disease, congestive heart failure, chronic obstructive pulmonary disease, chronic kidney disease), previous coronary artery bypass grafting or percutaneous transluminal coronary intervention, previous CEA or carotid artery stenting, degree of ipsilateral stenosis, the presence of contralateral occlusion, and preoperative medications. Intergroup differences between the treatment groups and differences in the perioperative outcomes were tested using the McNemar test for categorical variables and the paired t test or Wilcoxon matched pairs signed rank test for continuous variables, as appropriate. The relative risk (RR) and 95% confidence intervals (CIs) were estimated as the ratio of the probability of the outcome event for the patients treated within each treatment group. RESULTS: A total of 65,337 patients were included. Of the 65,337 patients, 59,664 had undergone carotid revascularization under GA (91%). When performed with LRA, TCAR and CEA had similar rates of stroke, death, and MI. However, when performed with GA, patients undergoing TCAR had a 50% decreased risk of MI compared with those undergoing CEA under GA (0.5% vs 1.0%; RR, 0.50; 95% CI, 0.32-0.80; P < .01). When stratified by symptomatic status, patients undergoing TCAR with GA for symptomatic carotid disease had a 67% decreased risk of MI compared with those undergoing CEA with GA for symptomatic disease (0.4% vs 1.2%; RR, 0.33; 95% CI, 0.15-0.75; P < .01). In contrast, no difference was found in the risk of MI between patients undergoing CEA vs TCAR for asymptomatic carotid disease (0.6% vs 0.9%; RR, 0.64; 95% CI, 0.37-1.14; P = .13). CONCLUSIONS: The results from the present study have confirmed previous studies suggesting that TCAR confers a lower risk of MI compared with CEA. However, our findings demonstrated no differences in the MI rates between TCAR and CEA when performed with LRA. Patients undergoing TCAR under GA had lower rates of MI compared with patients undergoing CEA under GA. When stratified by symptomatic status, the benefit of TCAR persisted only for the symptomatic patients.

Aortic Intimo-intimal Intussusception: A Pooled Analysis of Published Reports.

AIM: Aortic intimo-intimal intussusception (AoII) is a rare manifestation of aortic dissection with high mortality. This study aimed to obtain a comprehensive understanding of AoII. METHODS: Three databases (PubMed, Scopus, Embase) were searched with predefined search terms ["intimal intussusception", "aortic intussusception", "(circumferential) AND (intimal dissection)" and "(circumferential) AND (aortic dissection)"]. Demographics, clinical manifestations, imaging methods, therapies, and follow-up data were recorded and analyzed. RESULTS: The literature search finally identified 81 papers comprising 87 patients (Mean age: 53.7 ± 14.9 years old; male: n = 63). According to morphologic criteria (orientation of AoII intimal flap), patients were divided into three groups: antegrade (n = 37), retrograde (n = 49) and bidirectional (n = 1) orientation. The most frequent symptoms in antegrade group were chest pain (62.2%), syncope (27%), and unconsciousness (21.6%), while in retrograde group, they were chest pain (71.4%), dyspnea (20.4%), and back pain (16.3%). Regarding applied imaging modalities, 67.5% of patients in antegrade group were diagnosed with≥2 methods, comparing with 87.7% in retrograde group. A total of 21 patients (24.1%) with AoII finally died, among which 13.8% (12/87) died before surgery. CONCLUSION: AoII is a rare form of aortic dissection with high mortality. Antegrade orientation of the intima flap was more accompanied with neurological disorders and asymmetric blood pressure, while retrograde orientation mostly manifested with aortic regurgitation. Application of multiple imaging examinations may detect this rare entity in time.

Surgery and Endovascular Management in Patients With Takayasu's Arteritis: A Ten-Year Retrospective Study.

BACKGROUND: Takayasu's arteritis (TA) is an uncommon chronic vasculitis, and there is a lack of long-term large cohort studies regarding the optimal revascularization outcomes of patients with TA. METHODS: One hundred and sixteen patients with TA who underwent surgery or endovascular repair over a 10-year period were studied retrospectively. One hundred and fifty-four vascular procedures were performed consisting of 69 open and 85 endovascular repairs. RESULTS: After a mean follow-up period of 48.5 ± 38.5 months, three cases each of cerebrovascular accident (CVA) and death occurred in the open repair group while two cases of CVA and 4 deaths were observed in the endovascular repair group. At 1, 3, 5, and 10 years of follow-up, the primary patency rates were 97.3%, 86.2%, 70.5%, and 48.8% in the open repair group and 93.3%, 73.1%, 57.5%, and 31.8% in the endovascular repair group, respectively. The primary assisted patency rates were 98.2%, 90.3%, 73.2%, and 47.2% in the open repair group and 95%, 81%, 64.4%, and 35% in the endovascular repair group, respectively. The secondary patency rates were 98.2%, 96.1%, 83.5%, and 56.2% in the open repair group and 98.7%, 86%, 71.2%, and 44.9% in the endovascular repair group, respectively. The cumulative survival rates were 96.9%, 96.9%, 96.9%, and 90% in the open repair group and 97.4%, 97.4%, 88%, and 79.2% in the endovascular repair group, respectively. CONCLUSIONS: Both surgical repair and endovascular management are safe and efficient modes of treatment of TA. Surgical repair showed long-term durability, and it is suitable for complex lesions and failed cases of endovascular management.

Combined analysis of circRNA and mRNA profiles and interactions in patients with Diabetic Foot and Diabetes Mellitus.

In order to elucidate the pathogenesis and explore new biomarkers for diabetes and diabetic foot (DF), an analysis using RNA sequencing affords broader insights into gene expression regulatory networks in DF. To better explore the molecular basis of DF, we carried out an analysis of circular RNA (circRNA) and messenger RNA (mRNA) expression profiles of serum samples from DF patients and diabetes mellitus (DM) patients. The potential roles and interactions of differentially expressed circRNAs and mRNAs were classified by gene ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analyses. Compared with diabetes patients, 279 mRNAs were upregulated and 353 mRNAs were downregulated in the serum of DF patients, and 33 circRNAs were differently expressed. The differential genes at the nodes of the interaction network were screened, and TLR6 RUNX1 and ST2 were found to be related to the progression of diabetes and DF. The enrichment pathway analysis revealed that the lysosomal pathway played a critical role in the occurrence and development of DF. TLR6, RUNX1, and ST2 mRNA expressions and the lysosomal pathway may be involved in the pathogenesis of diabetes and DF. In addition, methane metabolism and Chagas disease pathways were observed in the occurrence and development of DF, which is a new discovery in this study. This study provides clues on the molecular mechanisms of DF at the circRNA and mRNA levels.

Management of Extracranial Carotid Artery Aneurysms: A 6-Year Case Series.

BACKGROUND We discuss the presentation and management of extracranial carotid artery aneurysms (ECAAs) and to develop a new type of classification. MATERIAL AND METHODS A retrospective review of 35 ECAAs patients who were admitted in our institution from January 2010 to June 2016 was conducted. The mean follow-up period was 25.58±22.13 months. RESULTS During the study period, 35 aneurysms were diagnosed and treated (mean age, 50.8±15.6 years; 15 men). There were 28 true aneurysms, 5 false aneurysms, and 2 dissecting aneurysms. A total of 16 patients with true aneurysms underwent open surgical treatment (group 1), whereas 15 received endovascular management, including all false and dissecting aneurysms (group 2). The remaining 4 true aneurysms were treated with hybrid operation (group 3). The patency rates of groups 1, 2, and 3 were 100%, 93.3%, and 100%, respectively. According to the Peking Union Medical College Hospital (PUMCH) Classification, all 24 cases of type Ia aneurysms were treated by either open surgery and/or endovascular treatment, whereas all 3 type Ib cases were treated solely by open surgery. All 5 type IIa patients were treated by endovascular treatment, with the exception of 1 failure that was transferred to hybrid operation. All 3 type IIb patients were treated by hybrid operation. CONCLUSIONS Open surgery was more frequently feasible in true aneurysms, and endovascular surgery was the first choice for false and dissecting aneurysms. Hybrid operation was available for complicated cases. The PUMCH classification may be helpful for selection of management strategies for ECAAs.

Endovascular Repair of Complex Aortoiliac Aneurysm with the Sandwich Technique in Sixteen Patients.

BACKGROUND: This study aimed to evaluate the safety and efficiency of the sandwich technique in endovascular repair of complex aortoiliac aneurysm. METHODS: Sixteen patients (mean age 69.6 years, ranging from 58 to 78 years) with complex aortoiliac aneurysm were studied retrospectively from October 2013 to September 2017 in two vascular centers of teaching hospitals. Computed tomography angiography (CTA) was performed to make individual therapy. They were all performed endovascular repair with sandwich technique, including one with the sandwich, chimney, and fenestrated techniques during the same procedure. All patients were followed up at 1 month, 3 months, 6 months, 12 months, and yearly thereafter with X-ray, ultrasound, and/or CTA. RESULTS: The initial technical success was 81.25%, and the assisted technical success was 100%. At final angiography, little flow of a type I and a type III endoleak was found in two patients with observation. Two type II endoleaks were also detected. During the perioperative period, two patients suffered myocardial infarction. One pulmonary infection and one urinary infection happened. No death or cerebrovascular events occurred. During the follow-up (mean 18 months, ranging from 2 to 45 months), three stent occlusions were detected. One case got reintervened for his external iliac artery stent thrombosis in the first month postoperatively. The other two were under observation. A readmission happened to one man for his right brachial artery pseudoaneurysm in the third month postoperatively. One patient died of nonaneurysmal related reason in the eighth month. No aneurysmal related death, rupture, or new endoleak was found. No paralysis, claudication, or bowel ischemia was complained of. The primary patency of the preserved branches were 94.7%, 92.0%, 92.0%, 92.0%, 92.0% separately in first, sixth, 12th, 24th, and 36th month. CONCLUSIONS: For patients who are not candidates for open surgery or conventional endovascular repair with complex aortoiliac aneurysm, the sandwich technique is a feasible alternative to management.

Simultaneous Multi-Supra-Aortic Artery Bypass Successfully Implemented in 17 Patients with Type I Takayasu Arteritis.

OBJECTIVE: Type I Takayasu arteritis is common in Chinese patients and usually leads to cerebral ischaemia. There are limited data regarding simultaneous multi-supra-aortic artery (SMSAA) bypass in patients with type I Takayasu arteritis. The present study shares experience of using this method. METHODS: Seventeen patients with Takayasu arteritis who received SMSAA bypass from June 2012 to March 2016 were included in this analysis. Demographic features and basic information were recorded. Follow up results, including major complications, patency rates, and survival rates, were also obtained. The EQ-5D questionnaire was also administered to evaluate the quality of life of patients. RESULTS: Among these 17 patients, there were 77 supra-aortic arteries affected by TA and 37 arteries were reconstructed, 10 with great saphenous vein and 27 with artificial blood vessels. All the operations were technical successes and the mean operation time was 396.6 ± 93.4 min. The patients were followed for a mean of 25.2 ± 12.3 months. Two graft restenoses were found, and both were successfully recanalised by balloon dilatation. One patient suffered a minor stroke but was free from obvious sequelae. No major complications, recurrent symptoms, or deaths occurred during the follow up period. The EQ-5D questionnaire scores were significantly improved after the operation compared with the pre-operative scores (87.14 ± 8.25 vs. 58.93 ± 14.4, p < .01), and all the patients enjoyed a satisfactory quality of life. CONCLUSION: SMSAA bypass in type I Takayasu arteritis can be effectively and safely performed with rigorous peri-operative management. Maintaining the patency of the bypass graft relieves the symptoms of cerebral ischaemia and helps sustain patients' quality of life.

Human Umbilical Cord Blood CD34+Cells InducedAngiogenesis in Ischemic Limb of Mice.

Objective To observe the effect of the expanded human umbilical cord blood CD34+cells in ischemic limb of mice and analyse the relationship between the CD34+cells and angiogenesis. Methods Human umbilical cord blood was collected and CD34+cells were separated for expanding. Mice limbs ischemia models were established (n=15) and randomly divided into three groups:expanded CD34+cells group (n=5),fresh CD34+cells group (n=5),and control group(n=5). CD34+cells were detected by DiI dye tracing and antihuman nuclear antigen antibody(HNA) immunohistochemical staining. The improvement of blood reperfusion was evaluated by indicators including limb temperature,CD31 staining,and transforming growth factor-ß1 (TGF-ß1) mRNA expression. Results On days 14 (t=5.421,P=0.001;t=0.616,P=0.000) and 28(t=10.780,P=0.000; t=12.123,P=0.000),both expanded CD34+cells group and fresh CD34+cells group enjoyed better temperature improvement. Days 28 later,the vascular densities in the expanded CD34+cells group and the fresh CD34+cells group were 592.3±24.6 (t=26.386,P=0.000) and 530.7±25.5 (t=21.502,P=0.000),which were significantly higher than that in control group 219.7±19.9. The TGF-ß1 mRNA expression in the expanded CD34+cells group and the fresh CD34+cells group were (0.578±0.050) copies (t=12.376,P=0.000) and (0.504±0.080) copies (t=7.098,P=0.000),both over control group [(0.224±0.040)copies]. Conclusions In vitro culture of cord blood CD34+cells can emigrate to ischemic zone and induce angiogenesis to alleviate ischemia. Thus,it may provide a treatment option for lower limb ischemia.

Engineering M2-type macrophages with a metal polyphenol network for peripheral artery disease treatment.

Functional cell treatment for critical limb ischemia is limited by cell viability loss and dysfunction resulting from a harmful ischemic microenvironment. Metal-polyphenol networks have emerged as novel cell delivery vehicles for protecting cells from the detrimental ischemic microenvironment and prolonging the survival rate of cells in the ischemic microenvironment. M2 macrophages are closely related to tissue repair, and they secrete anti-inflammatory factors that contribute to lesion repair. However, these cells are easily metabolized in the body with low efficiency. Herein, M2 macrophages were decorated with a metal‒polyphenol network that contains copper ions and epigallocatechin gallate (Cu-EGCG@M2) to increase cell survival and therapeutic potential. Cu-EGCG@M2 synergistically promoted angiogenesis through the inherent angiogenesis effect of M2 macrophages and copper ions. We found that Cu-EGCG@M2 increased in vitro viability and strengthened the in vivo therapeutic effect on the ischemic hindlimbs of mice, which promoted the recovery of blood and muscle regeneration, resulting in superior limb salvage. These therapeutic effects were ascribed to the increased survival rate and therapeutic period of M2 macrophages, as well as the ameliorated microenvironment at the ischemic site. Additionally, Cu-EGCG exhibited antioxidant, anti-inflammatory, and proangiogenic effects. Our findings provide a feasible option for cell-based treatment of CLI.

Endovascular repair of acute vs. subacute uncomplicated type B aortic dissection: a systematic review and meta-analysis.

Objective: This study aimed to conduct a meta-analysis evaluating the optimal timing for endovascular repair of acute versus subacute uncomplicated Type B Aortic Dissection. Method: PubMed, EMBASE, web of science and Cochrane Library was interrogated to identify Electronic bibliographic studies updated to January 2023 to collect studies compared the clinical outcomes of endovascular repair for Acute Versus Subacute Uncomplicated Type B Aortic Dissection. Data were aggregated as pooled odds ratios (OR) using the fixed or random effects models according to the significance of heterogeneity, Pooled odds ratios (OR) were calculated by RevMan 5.3 and applied with fixed or random-effect models. Result: A comprehensive literature search found 322 citations published and finally among them 6 studies containing 3,769 patients (acute group 2,642, subacute group 1,127) were included in review. There is an increased risk of 30-day complications (OR = 1.51,95%CI,1.26-1.81) 30-day mortality (OR = 2.39,95%CI, 1.55-3.67) and 1-year mortality (OR = 1.71,95%CI,1.27-2.30) for an acute uTBAD group compared to subacute ones. Similarly, reintervention was more likely in the acute group than in the subacute group (OR = 1.42,95%CI,1.05-1.91). However, no significant differences were found in long-term mortality. Conclusion: This meta-analysis confirmed that there was no significant difference in the long-term prognosis between the acute and subacute phases in the timing of surgery. However, considering the high incidence of complications, high re-intervention rate and one-year mortality probably caused by high intima fragility in the acute phase, endovascular repair at subacute phase appears to favorably compare with acute strategy. But future studies with adequate patient numbers and longer-term follow-up are necessary to further verify the study conclusion. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021247609, identifier PROSPERO CRD42021247609.

The genetic correlation and causal association between key factors that influence vascular calcification and cardiovascular disease incidence.

Background: Serum calcium (Ca), vitamin D (VD), and vitamin K (VK) levels are key determinants of vascular calcification, which itself impacts cardiovascular disease (CVD) risk. The specific relationships between the levels of these different compounds and particular forms of CVD, however, remain to be fully defined. Objective: This study was designed to explore the associations between these serum levels and CVDs with the goal of identifying natural interventions capable of controlling vascular calcification and thereby protecting against CVD pathogenesis, extending the healthy lifespan of at-risk individuals. Methods: Linkage disequilibrium score (LDSC) regression and a two-sample Mendelian randomization (MR) framework were leveraged to systematically examine the causal interplay between these serum levels and nine forms of CVD, as well as longevity through the use of large publically accessible Genome-Wide Association Studies (GWAS) datasets. The optimal concentrations of serum Ca and VD to lower CVD risk were examined through a restrictive cubic spline (RCS) approach. Results: After Bonferroni correction, the positive genetic correlations were observed between serum Ca levels and myocardial infarction (MI) (p = 1.356E-04), as well as coronary artery disease (CAD) (p = 3.601E-04). Negative genetic correlations were detected between levels of VD and CAD (p = 0.035), while elevated VK1 concentrations were causally associated with heart failure (HF) [odds ratios (OR) per 1-standard deviation (SD) increase: 1.044], large artery stroke (LAS) (OR per 1-SD increase: 1.172), and all stroke (AS) (OR per 1-SD increase: 1.041). Higher serum Ca concentrations (OR per 1-SD increase: 0.865) and VD levels (OR per 1-SD increase: 0.777) were causally associated with reduced odds of longevity. These findings remained consistent in sensitivity analyses, and serum Ca and VD concentrations of 2.376 mmol/L and 46.8 nmol/L, respectively, were associated with a lower CVD risk (p < 0.001). Conclusion: Our findings support a genetic correlation between serum Ca and VD and CVD risk, and a causal relationship between VK1 levels and CVD risk. The optimal serum Ca (2.376 mmol/L) and VD levels (46.8 nmol/L) can reduce cardiovascular risk.

Design and Protocol for Beijing Hospital Takayasu Arteritis (BeTA) Biobank.

BACKGROUND: Although hundreds of studies have been conducted, our understanding of the pathogenesis, indications for surgical intervention, and disease markers of Takayasu arteritis (TAK) are still limited. Collection of biological specimens, clinical data and imaging data will facilitate translational research and clinical studies. In this study, we aim to introduce the design and protocol for the Beijing Hospital Takayasu Arteritis (BeTA) Biobank. METHODS: Based in the Department of Vascular Surgery of Beijing Hospital and Beijing Hospital Clinical Biological Sample Management Center, the BeTA Biobank is composed of clinical data and sample data from patients with TAK requiring surgical treatment. All clinical data of participants are collected, including demographic characteristics, laboratory tests, imaging results, operation information, perioperative complications, follow-up data, etc. Both blood samples including plasma, serum and cells, and vascular tissues or perivascular adipose tissue are collected and stored. These samples will promote the establishment of a multiomic database for TAK and help to identify disease markers and to explore potential targets for specific future drugs for TAK.

Varicose Veins and Risk of Venous Thromboembolic Diseases: A Two-Sample-Based Mendelian Randomization Study.

Background: Varicose veins are found to be associated with increased risk of venous thromboembolism (VTE) in many observational studies, but whether varicose veins are causally associated with VTE remains unclear. Therefore, we used a series of Mendelian randomization (MR) methods to investigate that association. Methods: 23 independent single-nucleotide polymorphisms (SNPs) for varicose veins were obtained from the Pan UK Biobank analysis. The outcomes datasets for deep vein thrombosis (DVT), pulmonary embolism (PE) and venous thromboembolism (VTE) were obtained from the FinnGen study. Before analysis, body mass index (BMI) and height were included as confounders in our MR model. Basic MR [inverse-variance weighted (IVW), weight-median, penalized weighted-median and MR-Egger methods] and MR-PRESSO were performed against each outcome using the whole SNPs and SNPs after excluding those associated with confounders. If causal associations were suggested for any outcome, a basic MR validation analysis, a multivariable MR analysis with BMI and height, a Causal Analysis Using Summary Effect estimates (CAUSE), and a two-step MR analysis with BMI and height, would follow. Results: Using 21 qualified SNPs, the IVW method (OR: 1.173, 95% CI: 1.070-1.286, p < 0.001, FDR = 0.002), the weighted median method (OR: 1.255, 95% CI: 1.106-1.423, p < 0.001, FDR = 0.001), the penalized weighted median method (OR: 1.299, 95% CI: 1.128-1.495, p < 0.001, FDR = 0.001) and the MR-PRESSO (OR: 1.165, 95% CI: 1.067-1.273, p = 0.003, FDR = 0.009) suggested potential causal effect of varicose veins on DVT, but no cause effect was found for PE and VTE. Excluding SNPs associated with confounders yielded similar results. The causal association with DVT was validated using a self-reported DVT cohort (IVW, OR: 1.107, 95% CI: 1.041-1.178, p = 0.001). The causal association maintained after adjustment for height (OR = 1.105, 95% CI: 1.028-1.188, p = 0.007), BMI (OR = 1.148, 95% CI: 1.059-1.244, p < 0.001) and them both (OR = 1.104, 95% CI: 1.035-1.177, p = 0.003). The causal association also survived the strict CAUSE (p = 0.018). Finally, in two-step MR, height and BMI were found to have causal effects on both varicose veins and DVT. Conclusion: Genetically predicted varicose veins may have a causal effect on DVT and may be one of the mediators of obesity and taller height that predispose to DVT.

Identification of ITGAX and CCR1 as potential biomarkers of atherosclerosis via Gene Set Enrichment Analysis.

OBJECTIVE: Atherosclerosis (AS) is a life-threatening disease in aging populations worldwide. However, the molecular and gene regulation mechanisms of AS are still unclear. This study aimed to identify gene expression differences between atheroma plaques and normal tissues in humans. METHODS: The expression profiling dataset GSE43292 was obtained from the Gene Expression Omnibus (GEO) dataset. The differentially expressed genes (DEGs) were identified between the atheroma plaques and normal tissues via GEO2R, and functional annotation of the DEGs was performed by GSEA. STRING and MCODE plug-in of Cytoscape were used to construct a protein-protein interaction (PPI) network and analyze hub genes. Finally, quantitative polymerase chain reaction (qPCR) was performed to verify the hub genes. RESULTS: Overall, 134 DEGs were screened. Functional annotation demonstrated that these DEGs were mainly enriched in sphingolipid metabolism, apoptosis, lysosome, and more. Six hub genes were identified from the PPI network: ITGAX, CCR1, IL1RN, CXCL10, CD163, and MMP9. qPCR analysis suggested that the relative expression levels of the six hub genes were significantly higher in AS samples. CONCLUSIONS: We used bioinformatics to identify six hub genes: ITGAX, CCR1, IL1RN, CXCL10, CD163, and MMP9. These hub genes are potential promising diagnostic and therapeutic targets for AS.

Acute or Subacute, the Optimal Timing for Uncomplicated Type B Aortic Dissection: A Systematic Review and Meta-Analysis.

Objective: To evaluate the optimal timing (acute or subacute) of thoracic endovascular aortic repair (TEVAR) for uncomplicated B aortic dissection (uTBAD) through a systematic review and meta-analysis. Method: A comprehensive literature search was undertaken across three major databases (EMBASE/Medline, PubMed, and Cochrane Library) and was assessed until November 2021 to identify studies reporting the outcomes of TEVAR utilized to treat patients with uTBAD. The continuous variables were compared between the two groups using t-test and the categorical variables were compared using the χ2-test. A meta-analysis was used to produce pooled odds ratios for early and follow-up outcomes. The random effects models were applied. A statistical analysis was performed using R software v.4.1. Result: A comprehensive literature search found 490 citations published within the predetermined time span of the analysis. Three studies including 1,193 patients (acute group 718, subacute group 475) were finally included for downstream meta-analysis. An acute uTBAD group presented with higher rates both in 30-day complications (20.5 vs. 13.7%; p = 0.014) and mortality (4.6 vs. 1.3%; p = 0.004) than subacute group. The respiratory complications were significantly higher in the acute group than in the subacute group (10.8 vs. 5.0%; p = 0.015). The procedure success rate (90.8 vs. 93.6%; p = 0.329), the follow-up mortality (7.7 vs. 7.6%; p = 1) and dissection-related late mortality (3.9 vs. 5.3%; p = 0.603) showed no significant difference. Conclusion: Our meta-analysis suggested that despite significantly higher 30-day complications and 30-day mortality in the acute uTBAD group, there was no significant difference in the follow-up mortality between the two groups. Systematic Review Registration: PROSPERO, identifier: CRD42021247609.