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.

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.

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.

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.

Effect of Antiplatelet Agents on Abdominal Aortic Aneurysm Process: A Systematic Review and Meta-Analysis.

Background: This systematic review and meta-analysis aims to investigate whether antiplatelet agents are associated with the reduction, expansion, and rupture of abdominal aortic aneurysm (AAA). Methods: A thorough exploration was conducted on four prominent databases, namely EMBASE, Ovid, PubMed, and Scopus, to identify studies that reported the influence of antiplatelet agents on the sac development of AAA. The assessment was carried out until March 2023. R software v.4.1 was used for statistical analysis. Results: After reviewing 13 publications which included a total of 5392 patients (1446 in the antiplatelet group and 2540 in the control group), a meta-analysis was conducted. The results of the analysis revealed that there was no significant difference in the annual growth rate of AAA diameter between those who received antiplatelet agents and those who did not (mean difference (MD) = -0.04, 95% CI = [-0.37, 0.30]; heterogeneity: p < 0.01, I 2 = 91%, τ 2 = 0.1278). Additionally, there was no difference in the number of patients who experienced aneurysm diameter expansion between the two groups, significantly (odds ratio (OR) = 0.96, 95% CI = [0.41, 2.25]; heterogeneity: p < 0.01, I 2 = 78%, τ 2 = 0.5849). Conclusions: Antiplatelet agents do not affect AAA's reduction, expansion, or rupture. There is no benefit to AAA patients taking antiplatelet agents for the purpose of slowing down growth rates of sac diameter.

SGLT1/2 as the potential biomarkers of renal damage under Apoe-/- and chronic stress via the BP neural network model and support vector machine.

Background: Chronic stress (CS) could produce negative emotions. The molecular mechanism of SGLT1 and SGLT2 in kidney injury caused by chronic stress combined with atherosclerosis remains unclear. Methods: In total, 60 C57BL/6J mice were randomly divided into four groups, namely, control (CON, n = 15), control diet + chronic stress (CON+CS, n = 15), high-fat diet + Apoe-/- (HF + Apoe-/-, n = 15), and high-fat diet + Apoe-/- + chronic stress (HF+Apoe-/- + CS, n = 15) groups. The elevated plus maze and open field tests were performed to examine the effect of chronic stress. The expression of SGLT1 and SGLT2 in the kidney was detected. The support vector machine (SVM) and back propagation (BP) neural network model were constructed to explore the predictive value of the expression of SGLT1/2 on the renal pathological changes. The receiver operating characteristic (ROC) curve analysis was used. Results: A chronic stress model and atherosclerosis model were constructed successfully. Edema, broken reticular fiber, and increased glycogen in the kidney would be obvious in the HF + Apoe-/- + CS group. Compared with the CON group, the expression of SGLT1/2 in the kidney was upregulated in the HF + Apoe-/- + CS group (P < 0.05). There existed positive correlations among edema, glycogen, reticular fiber, expression of SGLT1/2 in the kidney. There were higher sensitivity and specificity of diagnosis of SGLT1/2 for edema, reticular fiber, and glycogen in the kidney. The result of the SVM and BP neural network model showed better predictive values of SGLT1 and SGLT2 for edema and glycogen in the kidney. Conclusion: In conclusion, SGLT1/2 might be potential biomarkers of renal damage under Apoe-/- and chronic stress, which provided a potential research direction for future related explorations into this mechanism.

Corrigendum to "ROS-responsive nanoparticle-mediated delivery of CYP2J2 gene for therapeutic angiogenesis in severe hindlimb ischemia" [Materials Today Bio 13(2022) 100192].

[This corrects the article DOI: 10.1016/j.mtbio.2021.100192.].

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.

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.

A Potential Target for Clinical Atherosclerosis: A Novel Insight Derived from TPM2.

Atherosclerosis (AS) is a potential inducer of numerous cardio-cerebrovascular diseases. However, little research has investigated the expression of TPM2 in human atherosclerosis samples. A total of 34 clinical samples were obtained, including 17 atherosclerosis and 17 normal artery samples, between January 2018 and April 2021. Bioinformatics analysis was applied to explore the potential role of TPM2 in atherosclerosis. Immunohistochemistry, immunofluorescence, and western blotting assays were used to detect the expression of TPM2 and α-SMA proteins. The mRNA expression levels of TPM2 and α-SMA were detected using RT-qPCR. A neural network and intima-media thickness model were constructed. A strong relationship existed between the intima-media thickness and relative protein expression of TPM2 (P<0.001, R=-0.579). The expression of TPM2 was lower in atherosclerosis than normal artery (P<0.05). Univariate logistic regression showed that TPM2 (OR=0.150, 95% CI: 0.026-0.868, P=0.034) had clear correlations with atherosclerosis. A neural network model was successfully constructed with a relativity of 0.94434. TPM2 might be an independent protective factor for arteries, and one novel biomarker of atherosclerosis.

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.

Recent Progress of Chronic Stress in the Development of Atherosclerosis.

With the development of the times, cardiovascular diseases have become the biggest cause of death in the global aging society, causing a serious social burden. Atherosclerosis is a chronic inflammatory disease, which can occur in large and medium-sized blood vessels in the whole body. It takes atherosclerotic plaque as the typical pathological change and endothelial injury as the core pathophysiological mechanism. It is the pathological basis of coronary heart disease, peripheral artery disease, cerebrovascular disease, and other diseases. Recent studies have shown that chronic stress plays an important role in the occurrence and development of atherosclerosis, endothelial injury, lipid metabolism, and chronic inflammation. This process involves a large number of molecular targets. It is usually the cause of atherosclerotic cardiovascular and cerebrovascular diseases. If chronic stress factors exist for a long time, patients have genetic susceptibility, and the combination of environmental factors triggers the pathogenesis, which may eventually lead to complete blockage of the blood vessels, unstable rupture of plaques, and serious adverse cardiovascular events. This paper reviews the role of chronic stress in the occurrence and development of atherosclerosis, focusing on the pathophysiological mechanism.

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.

ROS-responsive nanoparticle-mediated delivery of CYP2J2 gene for therapeutic angiogenesis in severe hindlimb ischemia.

With critical limb ischemia (CLI) being a multi-factorial disease, it is becoming evident that gene therapy with a multiple bio-functional growth factor could achieve better therapeutic outcomes. Cytochrome P450 epoxygenase-2J2 (CYP2J2) and its catalytic products epoxyeicosatrienoic acids (EETs) exhibit pleiotropic biological activities, including pro-angiogenic, anti-inflammatory and cardiovascular protective effects, which are considerably beneficial for reversing ischemia and restoring local blood flow in CLI. Here, we designed a nanoparticle-based pcDNA3.1-CYP2J2 plasmid DNA (pDNA) delivery system (nanoparticle/pDNA complex) composed of a novel three-arm star block copolymer (3S-PLGA-po-PEG), which was achieved by conjugating three-armed PLGA to PEG via the peroxalate ester bond. Considering the multiple bio-functions of CYP2J2-EETs and the sensitivity of the peroxalate ester bond to H2O2, this nanoparticle-based gene delivery system is expected to exhibit excellent pro-angiogenic effects while improving the high oxidative stress and inflammatory micro-environment in ischemic hindlimb. Our study reports the first application of CYP2J2 in the field of therapeutic angiogenesis for CLI treatment and our findings demonstrated good biocompatibility, stability and sustained release properties of the CYP2J2 nano-delivery system. In addition, this nanoparticle-based gene delivery system showed high transfection efficiency and efficient VEGF expression in vitro and in vivo. Intramuscular injection of nanoparticle/pDNA complexes into mice with hindlimb ischemia resulted in significant rapid blood flow recovery and improved muscle repair compared to mice treated with naked pDNA. In summary, 3S-PLGA-po-PEG/CYP2J2-pDNA complexes have tremendous potential and provide a practical strategy for the treatment of limb ischemia. Moreover, 3S-PLGA-po-PEG nanoparticles might be useful as a potential non-viral carrier for other gene delivery applications.

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.

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.

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.