Current Perspective and Strategy on Management of Spontaneous Jugular Venous Ectasia: A Systematic Review.

BACKGROUND: Spontaneous jugular venous ectasia (SJVE) is characterized by dilation of the internal jugular vein (IJV) and external jugular vein. It is generally considered a benign anomaly. There is no accepted categorization for this disorder. METHODS: We conducted a case series study and a systematic review of available articles on SJVE to understand the main characteristics, clinicopathologic classifications, and therapeutic approaches. RESULTS: From January 2001 to December 2021, 14 patients in our hospital were analyzed. A total of 110 original articles (295 cases/311 lesions) were included in the systematic review. We proposed a classification and categorized SJVE into 4 main types (type I-IV) plus one (type V) in which the specific ectasia was located around the jugular bulb at the IJV. CONCLUSIONS: Conservative treatment is preferred for patients with type I (without thrombus) SJVE and asymptomatic patients who can be treated without anticoagulants. The therapeutic efficiency of surgery was high, and the best surgical modalities were chosen according to the type of SJVE.

LncRNA CRNDE regulates the proliferation and migration of vascular smooth muscle cells.

Restenosis after angioplasty or stent is a major clinical problem. While long noncoding RNAs (lncRNAs) are implicated in a variety of diseases, their role in restenosis is not well understood. This study aims to investigate how dysregulated lncRNAs and messenger RNAs (mRNAs) contribute to restenosis. By microarray analysis, we identified 202 lncRNAs and 625 mRNAs (fold change > 2.0, p < 0.05) differentially expressed between the balloon-injured carotid artery and uninjured carotid artery in the rats. Among differentially expressed lncRNAs, LncRNA CRNDE had the highest fold change and the change was validated by reverse transcription polymerase chain reaction. We found that LncRNA CRNDE was significantly upregulated in injured rat carotid artery and vascular smooth muscle cells (VSMCs) stimulated by platelet-derived growth factor-BB (PDGF-BB). Knockdown of LncRNA CRNDE by small interference RNA significantly inhibited PDGF-BB stimulated proliferation and migration of VSMCs. Moreover, knockdown of LncRNA CRNDE attenuated PDGF-BB-induced phenotypic change of VSMCs. Taken together, our study reveals a novel mechanoresponsive LncRNA CRNDE which may be a therapeutic target for restenosis.

Pterostilbene alleviates abdominal aortic aneurysm via inhibiting macrophage pyroptosis by activating the miR-146a-5p/TRAF6 axis.

Pterostilbene (PTE), a natural stilbene found in blueberries and several varieties of grapes, has several pharmacological activities, including anti-inflammatory and antioxidative activities. However, its role in abdominal aortic aneurysm (AAA), which is a severe inflammatory vascular disease, remains incompletely understood. In this study, we investigated the protective effects of natural stilbene PTE on AAA formation and the underlying mechanism. Two AAA mouse models (Ang II-induced model and PPE-induced model) were used to examine the effect of PTE on AAA formation. We showed that PTE administration attenuated AAA formation in mice. Furthermore, we found that PTE significantly inhibited inflammatory responses in mouse aortas, as PTE suppressed macrophage pyroptosis and prevented macrophage infiltration in aortas, resulting in reduced expression of pro-inflammatory cytokines in aortas. We also observed similar results in LPS + ATP-treated Raw 264.7 cells (a macrophage cell line) and primary peritoneal macrophages in vitro. We showed that pretreatment with PTE restrained inflammatory responses in macrophages by inhibiting macrophage pyroptosis. Mechanistically, miR-146a-5p and TRAF6 interventions in vivo and in vitro were used to investigate the role of the miR-146a-5p/TRAF6 axis in the beneficial effect of PTE on macrophage pyroptosis and AAA. We found that PTE inhibited macrophage pyroptosis by miR-146a-5p-mediated suppression of downstream TRAF6 expression. Moreover, miR-146a-5p knockout or TRAF6 overexpression abrogated the protective effect of PTE on macrophage pyroptosis and AAA formation. These findings suggest that miR-146a-5p/TRAF6 axis activation by PTE protects against macrophage pyroptosis and AAA formation. PTE might be a promising agent for preventing inflammatory vascular diseases, including AAA.

The in vivo blood compatibility of bio-inspired small diameter vascular graft: effect of submicron longitudinally aligned topography.

BACKGROUND: Cardiovascular disease is the leading cause of deaths worldwide and the arterial reconstructive surgery remains the treatment of choice. Although large diameter vascular grafts have been widely used in clinical practices, there is an urgent need to develop a small diameter vascular graft with enhanced blood compatibility. Herein, we fabricated a small diameter vascular graft with submicron longitudinally aligned topography, which mimicked the tunica intima of the native arterial vessels and were tested in Sprague-Dawley (SD) rats. METHODS: Vascular grafts with aligned and smooth topography were prepared by electrospinning and were connected to the abdominal aorta of the SD rats to evaluate their blood compatibility. Graft patency and platelet adhesion were evaluated by color Doppler ultrasound and immunofluorescence respectively. RESULTS: We observed a significant higher patency rate (p = 0.021) and less thrombus formation in vascular graft with aligned topography than vascular graft with smooth topography. However, no significant difference between the adhesion rates on both vascular grafts (smooth/aligned: 0.35‰/0.12‰, p > 0.05) was observed. Moreover, both vascular grafts had few adherent activated platelets on the luminal surface. CONCLUSION: Bionic vascular graft showed enhanced blood compatibility due to the effect of surface topography. Therefore, it has considerable potential for using in clinical application.

Ultrasound-guided intraoperative inferior vena cava stent implantation for treatment of acute hypotension during orthotopic liver transplantation.

Severe obstruction of inferior vena cava (IVC) outflow after orthotopic liver transplantation can result in persistent hypotension, leading to transplantation failure and intraoperative circulatory instability and can even threaten the patient's life. IVC stent implantation is a therapeutic approach to relieve the obstruction of IVC outflow. In the present report, we describe two cases of IVC stent implantation assisted by color Doppler ultrasound during orthotopic liver transplantation to manage the persistent hypotension caused by acute obstruction of IVC outflow. At 1 and 3 months of follow-up, the stent position was optimal, and the stent and IVC patency were satisfactory without thrombosis.

Microarray Expression Profile and Bioinformatic Analysis of Circular RNA in Human Arteriosclerosis Obliterans.

Background: Arteriosclerosis obliterans (ASO) is the leading cause of nontraumatic lower-extremity amputations. Multiple researches have suggested that circular RNAs (circRNAs) played vital regulatory functions in cancer and cardiovascular disease. Nevertheless, the underlying effect and pathological mechanism of circRNAs in the formation and progression of ASO are still indistinct. Methods and Results: This study used microarray analysis to investigate the expression portrait of circRNAs in normal lower extremity arteries and ASO arteries. Bioinformatics analysis was conducted using the KEGG database to study the enrichment of differentially expressed circRNAs (DE circRNAs) and predict their functions. The accuracy of microarray assay was verified by evaluating expression of the top 5 upregulated and 5 downregulated circRNAs (raw density of normal group ≥200) using RT-qPCR. A circRNA-miRNA-mRNA interaction network was further predicted using software. Compared to the normal lower extremity group, the ASO arteries with HE and EVG staining presented hyperplastic fibrous membrane and luminal stenosis. A total of 12,735 circRNAs were identified, including 1196 DE circRNAs with 276 upregulated and 920 downregulated in ASO group based on |log2(FC)| > 1 and padj < 0.05. Among selected 10 circRNAs, RT-qPCR confirmed that hsa_circ_0003266, hsa_circ_0118936 and hsa_circ_0067161 were upregulated while hsa_circ_0091934 and hsa_circ_0092022 were downregulated in ASO group (p < 0.05). GO analysis presented that the DE circRNAs were primarily enriched in protein binding, intracellular part and organelle organization. KEGG pathway analysis indicated that MAPK signaling pathway, human T-cell leukemia virus 1 infection, proteoglycans in cancer were associated with the DE circRNAs. The circRNA-miRNA-mRNA interactive network revealed that both mRNAs and miRNAs linked to circRNAs played an indispensable role in ASO. Conclusion: This study described the expression portrait of circRNAs in human ASO arteries, and revealed the molecular background for further investigations of the circRNA regulatory mechanism in the formation and progression of ASO.

The in vivo performance of small-caliber nanofibrous polyurethane vascular grafts.

BACKGROUND: In a previous in vitro study, we confirmed that small-caliber nanofibrous polyurethane (PU) vascular grafts have favorable mechanical properties and biocompatibility. In the present study, we examined the in vivo biocompatibility and stability of these grafts. METHODS: Forty-eight adult male beagle dogs were randomly divided into two groups receiving, respectively, polyurethane (PU) or polytetrafluoroethylene (PTFE) grafts (n = 24 animals / group). Each group was studied at 4, 8, 12, and 24 weeks after graft implantation. Blood flow was analyzed by color Doppler ultrasound and computed tomography angiography. Patency rates were judged by animal survival rates. Coverage with endothelial and smooth muscle cells was characterized by hematoxylin-eosin and immunohistological staining, and scanning electron microscopy (SEM). RESULTS: Patency rates were significantly higher in the PU group (p = 0.02 vs. PTFE group). During the first 8 weeks, endothelial cells gradually formed a continuous layer on the internal surface of PU grafts, whereas coverage of PTFE graft by endothelial cells was inhomogeneous. After 12 weeks, neointimal thickness remained constant in the PU group, while PTFE group showed neointimal hyperplasia. At 24 weeks, some anastomotic sites of PTFE grafts became stenotic (p = 0.013 vs. PU group). Immunohistological staining revealed a continuous coverage by endothelial cells and an orderly arrangement of smooth muscle cells on PU grafts. Further, SEM showed smooth internal surfaces in PU grafts without thrombus or obvious neointimal hyperplasia. CONCLUSIONS: Small-caliber nanofibrous PU vascular grafts facilitate the endothelialization process, prevent excessive neointimal hyperplasia, and improve patency rates.

Integrative analysis prioritizes the relevant genes and risk factors for chronic venous disease.

OBJECTIVE: Chronic venous disease (CVD) refers to a range of symptoms resulting from long-term morphological and functional abnormalities of the venous system. However, the mechanism of CVD development remains largely unknown. Here, we aim to provide more information on CVD pathogenesis, prevention strategies, and therapy development through the integrative analysis of large-scale genetic data. METHODS: Genetic data were obtained from publicly accessible databases. We used different approaches, including Functional Mapping and Annotation, DEPICT, Sherlock, SMR/HEIDIS, DEPICT, and NetWAS to identify possible causal genes for CVD. Candidate genes were prioritized to further literature-based review. The differential expression of prioritized genes was validated by microarray from the Gene Expression Omnibus, a public genomics data repository and real-time quantitative polymerase chain reaction of varicose vein specimens. The causal relationships between risk factors and CVD were assessed using the two-sample Mendelian randomization approach. RESULTS: We identified 46 lead single-nucleotide polymorphisms and 26 plausible causal genes for CVD. Microarray data indicated differential expression of possible causal genes in CVD when compared with controls. The expression levels of WDR92, RSPO3, LIMA, ABCB10, DNAJC7, C1S, and CXCL1 were significantly downregulated (P < .05). PHLDA1 and SERPINE1 were significantly upregulated (P < .05). Dysregulated expression of WDR92, RSPO3, and CASZ1 was also found in varicose vein specimens by quantitative polymerase chain reaction. Two-sample Mendelian randomization suggested causative effects of body mass index (odds ratio [OR], 1.008; 95% confidence interval [CI], 1.005-1.010), standing height (OR, 1.009; 95% CI, 1.007-1.011), college degree (OR, 0.983; 95% CI, 0.991-0.976), insulin (OR, 0.858; 95% CI, 0.794-0.928), and metformin (OR, 0.944; 95% CI, 0.904-0.985) on CVD. CONCLUSIONS: Our study integrates genetic and gene expression data to make an effective risk gene prediction and etiological inferences for CVD. Prioritized candidate genes provide more insights into CVD pathogenesis, and the causative effects of risk factors on CVD that deserve further investigation.

IP-10/CXCR3 Axis Promotes the Proliferation of Vascular Smooth Muscle Cells through ERK1/2/CREB Signaling Pathway.

Excessive proliferation of vascular smooth muscle cells is one of the main pathological processes leading to atherosclerosis and intimal hyperplasia after vascular interventional therapy. Our previous study has shown that interferon-γ inducible protein-10 contributes to the proliferation of vascular smooth muscle cell. However, the underlying mechanisms remain unclear. Extracellular signal-regulated kinase 1/2, serine/threonine kinase Akt, and cAMP response element binding protein are signaling pathways, which are considered to play important roles in the processes of vascular smooth muscle cell proliferation. Moreover, chemokine receptor 3 and Toll-like receptor 4 are potential receptors of inducible protein-10 in this process. In the present study, IP-10 was found to directly induce vascular smooth muscle cell proliferation, and exposure to inducible protein-10 activated extracellular signal-regulated kinase 1/2, serine/threonine kinase, and cAMP response element binding protein signaling. Inhibitor of extracellular signal-regulated kinase 1/2, rather than inhibitor of serine/threonine kinase, inhibited the phosphorylation of cAMP response element binding protein and reduced inducible protein-10-stimulated vascular smooth muscle cell proliferation. Knockdown of cAMP response element binding protein by siRNA inhibited inducible protein-10-induced vascular smooth muscle cell proliferation. Moreover, anti-CXCR3 IgG, instead of anti-Toll-like receptor 4 IgG, reduced inducible protein-10-induced vascular smooth muscle cell proliferation and inducible protein-10-stimulated extracellular signal-regulated kinase 1/2 and cAMP response element binding protein activation. Together, these results indicate that inducible protein-10 promotes vascular smooth muscle cell proliferation via chemokine receptor 3 and activation of extracellular signal-regulated kinase 1/2 inducible protein-10-induced vascular smooth muscle cell proliferation. These data provide important targets for future studies to modulate atherosclerosis and restenosis after vascular interventional therapy.

Denervation in Femoral Artery-Ligated Hindlimbs Diminishes Ischemic Recovery Primarily via Impaired Arteriogenesis.

AIMS: Multiple factors regulate arteriogenesis. Peripheral nerves play a crucial role in vascular remodeling, but the function of peripheral nerves during arteriogenesis is obscure. Our study investigated the contribution of denervation to arteriogenesis during post-ischemic recovery from hindlimb femoral artery ligation. METHODS AND RESULTS: Sprague-Dawley rats were randomly allocated into four groups of normal control (NC), hindlimb ischemia (HI), hindlimb ischemia with denervation (HID) and hindlimb simple denervation (HD). Hindlimb ischemic recovery was assessed by clinical assessment and tibialis anterior muscle remodeling on day 28 post-surgery. Blood flow was determined by laser Doppler imaging on day 0, 3, 7, 14 and 28 post-surgery. Collateral number of hindlimb was observed by angiography and gracilis muscles were tested by immunostaining on day 7 and 28 post-surgery. Angiogenesis was accessed by counting CD31 positive capillaries in tibialis anterior muscles on day 28 post-surgery. Group HID showed impaired ischemic recovery compared with the other 3 groups and impaired blood flow recovery compared with group HI on day 28 post-surgery. The collateral number and capillary density of group HID were lower than group HI. The collateral diameter of both group HID and group HI significantly increased compared with group NC. However, the lumen diameter was much narrower and the vessel wall was much thicker in group HID than group HI. We also demonstrated that the thickened neointima of collaterals in group HID comprised of smooth muscle cells and endothelial cells. CONCLUSIONS: Denervation of the ligated femoral artery in the hindlimb impairs ischemic recovery via impaired perfusion. The possible mechanisms of impaired perfusion are lower collateral number, lower capillary density and most likely narrower lumen, which damage ischemic recovery. This study illustrates the crucial role of peripheral nerves in arteriogenesis using a model combined ischemia with denervation in hindlimb.

Scab-inspired cytophilic membrane of anisotropic nanofibers for rapid wound healing.

This work investigates the influence of cytophilic and anisotropic nanomaterials on accelerated cell attachment and directional migration toward rapid wound healing. Inspired by the anisotropic protein nanofibers in scab, a polyurethane (PU) nanofibrous membrane with an aligned structure was fabricated. The membrane showed good affinity for wound-healing-related cells and could guide cell migration in the direction of PU nanofibers. Also, the morphology and distribution of F-actin and paxillin of attached cells were influenced by the underlying nanofibers. The randomly distributed PU nanofibers and planar PU membrane did not show a distinct impact on cell migration. This scab-inspired cytophilic membrane is promising in applications as functional interfacial biomaterials for rapid wound healing, bone repair, and construction of neural networks.