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1.
Cells ; 13(19)2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39404400

RESUMO

Vascular access is an indispensable component of haemodialysis therapy for end-stage kidney disease patients. The arteriovenous fistula (AVF) is most common, but importantly, two-year failure rates are greater than fifty percent. AVF failure can occur due to a lack of suitable vascular remodelling, and inappropriate inflammation preventing maturation, or alternatively neointimal hyperplasia and vascular stenosis preventing long-term use. A comprehensive mechanistic understanding of these processes is still lacking, but recent studies highlight an essential role for inflammation from uraemia and the AVF itself. Inflammation affects each cell in the cascade of AVF failure, the endothelium, the infiltrating immune cells, and the vascular smooth muscle cells. This review examines the role of inflammation in each cell step by step and the influence on AVF failure. Inflammation resulting in AVF failure occurs initially via changes in endothelial cell activation, permeability, and vasoprotective chemokine secretion. Resultingly, immune cells can extravasate into the subendothelial space to release inflammatory cytokines and cause other deleterious changes to the microenvironment. Finally, all these changes modify vascular smooth muscle cell function, resulting in excessive and unchecked hyperplasia and proliferation, eventually leading to stenosis and the failure of the AVF. Finally, the emerging therapeutic options based off these findings are discussed, including mesenchymal stem cells, small-molecule inhibitors, and far-infrared therapies. Recent years have clearly demonstrated a vital role for inflammation in deciding the fate of the AVF, and future works must be centred on this to develop therapies for a hitherto unacceptably underserved patient population.


Assuntos
Fístula Arteriovenosa , Inflamação , Diálise Renal , Humanos , Diálise Renal/efeitos adversos , Inflamação/patologia , Fístula Arteriovenosa/patologia , Fístula Arteriovenosa/terapia , Animais , Rim/patologia , Falência Renal Crônica/terapia , Falência Renal Crônica/patologia , Derivação Arteriovenosa Cirúrgica/efeitos adversos
2.
Int J Mol Sci ; 25(17)2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-39273465

RESUMO

The number of patients with end-stage renal disease (ESRD) requiring hemodialysis is increasing worldwide. Although arteriovenous fistula (AVF) is the best and most important vascular access (VA) for hemodialysis, its primary maturation failure rate is as high as 60%, which seriously endangers the prognosis of hemodialysis patients. After AVF establishment, the venous outflow tract undergoes hemodynamic changes, which are translated into intracellular signaling pathway cascades, resulting in an outward and inward remodeling of the vessel wall. Outward remodeling refers to the thickening of the vessel wall and the dilation of the lumen to accommodate the high blood flow in the AVF, while inward remodeling is mainly characterized by intimal hyperplasia. More and more studies have shown that the two types of remodeling are closely related in the occurrence and development of, and jointly determining the final fate of, AVF. Therefore, it is essential to investigate the underlying mechanisms involved in outward and inward remodeling for identifying the key targets in alleviating AVF dysfunction. In this review, we summarize the current clinical diagnosis, monitoring, and treatment techniques for AVF dysfunction and discuss the possible pathological mechanisms related to improper outward and inward remodeling in AVF dysfunction, as well as summarize the similarities and differences between the two remodeling types in molecular mechanisms. Finally, the representative therapeutic targets of potential clinical values are summarized.


Assuntos
Fístula Arteriovenosa , Diálise Renal , Humanos , Fístula Arteriovenosa/metabolismo , Fístula Arteriovenosa/terapia , Fístula Arteriovenosa/patologia , Remodelação Vascular , Falência Renal Crônica/terapia , Falência Renal Crônica/patologia , Falência Renal Crônica/metabolismo , Derivação Arteriovenosa Cirúrgica/efeitos adversos , Animais , Hemodinâmica , Transdução de Sinais , Terapia de Alvo Molecular
3.
Cardiovasc Pathol ; 73: 107685, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39142442

RESUMO

BACKGROUND: To report the diagnosis and treatment of a rare disease of intravenous leiomyomatosis (IVL) originating from the uterus, growing in the inferior vena cava (IVC) and extending into the right atrium (RA) associated with a pelvic arteriovenous fistula (AVF). This is the first reported case of IVL in the IVC and RA with pulmonary benign metastasizing leiomyoma (PBML) secondary to a pelvic AVF despite the use of GnRH agonists in a nonmenopausal woman. CASE PRESENTATION: The patient was a 50-year-old premenopausal woman with a history of surgical resection for and antiestrogen conservative drug for pulmonary benign metastasizing leiomyoma (PBML) 5 years. The patient nevertheless developed IVL in the IVC, internal iliac vein and RA accompanied by AVF. Vaginal ultrasound combined with echocardiography and computerized tomographic venography imaging assists in the diagnosis of IVL combined with AVF, with histopathology and immunohistochemistry ultimately confirming the diagnosis. The patient ultimately was performed with a combination of hysterectomy, bilateral adnexectomy, and resection of tumors in the IVC and RA without cardiopulmonary bypass and sternotomy. CONCLUSION: BML may be difficult to control with incomplete removal of the uterus and ovaries even with the use of antiestrogenic medications, and medically induced AVF resulting from fibroid surgery may accelerate this process and the development of IVL.


Assuntos
Fístula Arteriovenosa , Átrios do Coração , Leiomiomatose , Neoplasias Pulmonares , Neoplasias Uterinas , Neoplasias Vasculares , Veia Cava Inferior , Humanos , Feminino , Veia Cava Inferior/patologia , Veia Cava Inferior/cirurgia , Veia Cava Inferior/diagnóstico por imagem , Pessoa de Meia-Idade , Neoplasias Uterinas/patologia , Neoplasias Uterinas/cirurgia , Fístula Arteriovenosa/cirurgia , Fístula Arteriovenosa/etiologia , Fístula Arteriovenosa/diagnóstico por imagem , Fístula Arteriovenosa/patologia , Átrios do Coração/patologia , Átrios do Coração/cirurgia , Átrios do Coração/diagnóstico por imagem , Leiomiomatose/patologia , Leiomiomatose/cirurgia , Leiomiomatose/diagnóstico por imagem , Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/patologia , Neoplasias Vasculares/patologia , Neoplasias Vasculares/cirurgia , Neoplasias Vasculares/diagnóstico por imagem , Neoplasias Cardíacas/secundário , Neoplasias Cardíacas/patologia , Neoplasias Cardíacas/cirurgia , Neoplasias Cardíacas/complicações , Resultado do Tratamento , Histerectomia , Veia Ilíaca/patologia , Veia Ilíaca/diagnóstico por imagem
4.
ACS Appl Mater Interfaces ; 16(26): 33159-33168, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38912610

RESUMO

In the context of arteriovenous fistula (AVF) failure, local delivery enables the release of higher concentrations of drugs that can suppress neointimal hyperplasia (NIH) while reducing systemic adverse effects. However, the radiolucency of polymeric delivery systems hinders long-term in vivo surveillance of safety and efficacy. We hypothesize that using a radiopaque perivascular wrap to deliver anti-NIH drugs could enhance AVF maturation. Through electrospinning, we fabricated multifunctional perivascular polycaprolactone (PCL) wraps loaded with bismuth nanoparticles (BiNPs) for enhanced radiologic visibility and drugs that can attenuate NIH─rosuvastatin (Rosu) and rapamycin (Rapa). The following groups were tested on the AVFs of a total of 24 Sprague-Dawley rats with induced chronic kidney disease: control (i.e., without wrap), PCL-Bi (i.e., wrap with BiNPs), PCL-Bi-Rosu, and PCL-Bi-Rapa. We found that BiNPs significantly improved the wraps' radiopacity without affecting biocompatibility. The drug release profiles of Rosu (hydrophilic drug) and Rapa (hydrophobic drug) differed significantly. Rosu demonstrated a burst release followed by gradual tapering over 8 weeks, while Rapa demonstrated a gradual release similar to that of the hydrophobic BiNPs. In vivo investigations revealed that both drug-loaded wraps can reduce vascular stenosis on ultrasonography and histomorphometry, as well as reduce [18F]Fluorodeoxyglucose uptake on positron emission tomography. Immunohistochemical studies revealed that PCL-Bi-Rosu primarily attenuated endothelial dysfunction and hypoxia in the neointimal layer, while PCL-Bi-Rapa modulated hypoxia, inflammation, and cellular proliferation across the whole outflow vein. In summary, the controlled delivery of drugs with different properties and mechanisms of action against NIH through a multifunctional, radiopaque perivascular wrap can improve imaging and histologic parameters of AVF maturation.


Assuntos
Bismuto , Ratos Sprague-Dawley , Rosuvastatina Cálcica , Sirolimo , Animais , Ratos , Sirolimo/química , Sirolimo/farmacologia , Rosuvastatina Cálcica/química , Rosuvastatina Cálcica/farmacologia , Rosuvastatina Cálcica/farmacocinética , Bismuto/química , Bismuto/farmacologia , Poliésteres/química , Masculino , Fístula Arteriovenosa/patologia , Nanopartículas Metálicas/química , Neointima/patologia , Nanopartículas/química , Humanos , Liberação Controlada de Fármacos
5.
Int J Mol Sci ; 25(11)2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38892351

RESUMO

Pulmonary arteriovenous malformations (PAVMs) are vascular anomalies resulting in abnormal connections between pulmonary arteries and veins. In 80% of cases, PAVMs are present from birth, but clinical manifestations are rarely seen in childhood. These congenital malformations are typically associated with Hereditary Hemorrhagic Telangiectasia (HHT), a rare disease that affects 1 in 5000/8000 individuals. HHT disease is frequently caused by mutations in genes involved in the TGF-ß pathway. However, approximately 15% of patients do not have a genetic diagnosis and, among the genetically diagnosed, more than 33% do not meet the Curaçao criteria. This makes clinical diagnosis even more challenging in the pediatric age group. Here, we introduce an 8-year-old patient bearing a severe phenotype of multiple diffuse PAVMs caused by an unknown mutation which ended in lung transplantation. Phenotypically, the case under study follows a molecular pattern which is HHT-like. Therefore, molecular- biological and cellular-functional analyses have been performed in primary endothelial cells (ECs) isolated from the explanted lung. The findings revealed a loss of functionality in lung endothelial tissue and a stimulation of endothelial-to-mesenchymal transition. Understanding the molecular basis of this transition could potentially offer new therapeutic strategies to delay lung transplantation in severe cases.


Assuntos
Células Endoteliais , Artéria Pulmonar , Veias Pulmonares , Telangiectasia Hemorrágica Hereditária , Humanos , Telangiectasia Hemorrágica Hereditária/genética , Telangiectasia Hemorrágica Hereditária/patologia , Criança , Artéria Pulmonar/anormalidades , Artéria Pulmonar/patologia , Veias Pulmonares/anormalidades , Veias Pulmonares/patologia , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Masculino , Mutação , Malformações Arteriovenosas/genética , Malformações Arteriovenosas/patologia , Malformações Arteriovenosas/metabolismo , Transição Epitelial-Mesenquimal/genética , Transplante de Pulmão , Fístula Arteriovenosa/patologia , Fístula Arteriovenosa/genética , Pulmão/patologia , Pulmão/irrigação sanguínea , Feminino
6.
Sci Rep ; 14(1): 13287, 2024 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-38858395

RESUMO

Clinical outcomes of arteriovenous fistulae (AVF) for hemodialysis remain inadequate since biological mechanisms of AVF maturation and failure are still poorly understood. Aortocaval fistula creation (AVF group) or a sham operation (sham group) was performed in C57BL/6 mice. Venous limbs were collected on postoperative day 7 and total RNA was extracted for high throughput RNA sequencing and bioinformatic analysis. Genes in metabolic pathways were significantly downregulated in the AVF, whereas significant sex differences were not detected. Since gene expression patterns among the AVF group were heterogenous, the AVF group was divided into a 'normal' AVF (nAVF) group and an 'outliers' (OUT) group. The gene expression patterns of the nAVF and OUT groups were consistent with previously published data showing venous adaptive remodeling, whereas enrichment analyses showed significant upregulation of metabolism, inflammation and coagulation in the OUT group compared to the nAVF group, suggesting the heterogeneity during venous remodeling reflects early gene expression changes that may correlate with AVF maturation or failure. Early detection of these processes may be a translational strategy to predict fistula failure and reduce patient morbidity.


Assuntos
Derivação Arteriovenosa Cirúrgica , Camundongos Endogâmicos C57BL , Remodelação Vascular , Animais , Camundongos , Masculino , Remodelação Vascular/genética , Feminino , Regulação para Baixo/genética , Veias/metabolismo , Diálise Renal , Fístula Arteriovenosa/genética , Fístula Arteriovenosa/metabolismo , Fístula Arteriovenosa/patologia , Regulação da Expressão Gênica , Perfilação da Expressão Gênica
7.
Nat Commun ; 15(1): 3743, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38702316

RESUMO

Arteriovenous fistulas (AVFs) are the most common vascular access points for hemodialysis (HD), but they have a high incidence of postoperative dysfunction, mainly due to excessive neointimal hyperplasia (NIH). Our previous studies have revealed a highly conserved LncRNA-LncDACH1 as an important regulator of cardiomyocyte and fibroblast proliferation. Herein, we find that LncDACH1 regulates NIH in AVF in male mice with conditional knockout of smooth muscle cell-specific LncDACH1 and in male mice model of AVF with LncDACH1 overexpression by adeno-associated virus. Mechanistically, silence of LncDACH1 activates p-AKT through promoting the expression of heat shock protein 90 (HSP90) and serine/arginine-rich splicing factor protein kinase 1 (SRPK1). Moreover, LncDACH1 is transcriptionally activated by transcription factor KLF9 that binds directly to the promoter region of the LncDACH1 gene. In this work, during AVF NIH, LncDACH1 is downregulated by KLF9 and promotes NIH through the HSP90/ SRPK1/ AKT signaling axis.


Assuntos
Proteínas de Choque Térmico HSP90 , Hiperplasia , Fatores de Transcrição Kruppel-Like , Miócitos de Músculo Liso , Neointima , Proteínas Proto-Oncogênicas c-akt , RNA Longo não Codificante , Animais , Humanos , Masculino , Camundongos , Fístula Arteriovenosa/metabolismo , Fístula Arteriovenosa/genética , Fístula Arteriovenosa/patologia , Proliferação de Células , Proteínas de Choque Térmico HSP90/metabolismo , Proteínas de Choque Térmico HSP90/genética , Fatores de Transcrição Kruppel-Like/metabolismo , Fatores de Transcrição Kruppel-Like/genética , Camundongos Endogâmicos C57BL , Camundongos Knockout , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/patologia , Neointima/patologia , Neointima/metabolismo , Fenótipo , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Serina-Treonina Quinases/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Transdução de Sinais
8.
Sci Rep ; 14(1): 4803, 2024 02 27.
Artigo em Inglês | MEDLINE | ID: mdl-38413764

RESUMO

To investigate the endothelialization of covered and bare stents deployed in the canine carotid arteries and subclavian arteries for treating experimental aneurysms and arteriovenous fistulas, twenty aneurysms were created in 10 dogs, and 20 fistulas in another 10 dogs. The Willis balloon-expandable covered stent and a self-expandable covered stent were used to treat these lesions, and a self-expandable bare stent was deployed in the subclavian artery for comparison. Followed up for up to 12 months, the gross observation, pathological staining, and scanning electronic microscopic data were analyzed. Two weeks after creation of animal model, thirty self-expandable covered stents and ten balloon-expandable covered stents were deployed. Fifteen bare stents were deployed within the left subclavian arteries. Twenty days after stenting, the aneurysm significantly shrank. At 6 months, the thrombi within the aneurysm cavity were organized. Three to 12 months later, most covered and bare stents were covered by a thin transparent or white layer of endothelial intima. Layers of intima or pseudomembrane were formed on the stent 20-40 days after stent deployment. Over three months, the pseudomembrane became organized, thinner, and merged into the vascular wall. Under scanning electronic microscopy, the surface of covered and bare stents had only deposition of collagen fibers and rare endothelial cells 20-40 days after stenting. From three to ten months, the endothelial cells on the internal surface of stent became mature, with spindle, stripe-like or quasi round morphology along the blood flow direction. Over time, the endothelial cells became mature. In conclusion, three months after deployment in canines' arteries, the self-expandable bare and covered stents have mostly been covered by endothelial cells which become maturer over time, whereas the balloon-expandable covered stents do not have complete coverage of endothelial cells at three months, especially for protruding stent struts and areas. Over time, the endothelialization will become mature.


Assuntos
Aneurisma , Fístula Arteriovenosa , Cães , Animais , Células Endoteliais , Aneurisma/cirurgia , Aneurisma/patologia , Stents/efeitos adversos , Artérias Carótidas/cirurgia , Artérias Carótidas/patologia , Fístula Arteriovenosa/patologia , Politetrafluoretileno
10.
Adv Healthc Mater ; 12(26): e2300960, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37395729

RESUMO

Bioresorbable perivascular scaffolds loaded with antiproliferative agents have been shown to enhance arteriovenous fistula (AVF) maturation by inhibiting neointimal hyperplasia (NIH). These scaffolds, which can mimic the three-dimensional architecture of the vascular extracellular matrix, also have an untapped potential for the local delivery of cell therapies against NIH. Hence, an electrospun perivascular scaffold from polycaprolactone (PCL) to support mesenchymal stem cell (MSC) attachment and gradual elution at the AVF's outflow vein is fabricated. Chronic kidney disease (CKD) in Sprague-Dawley rats is induced by performing 5/6th nephrectomy, then AVFs for scaffold application are created. The following groups of CKD rats are compared: no perivascular scaffold (i.e., control), PCL alone, and PCL+MSC scaffold. PCL and PCL+MSC significantly improve ultrasonographic (i.e., luminal diameter, wall-to-lumen ratio, and flow rate) and histologic (i.e., neointima-to-lumen ratio, neointima-to-media ratio) parameters compared to control, with PCL+MSC demonstrating further improvement in these parameters compared to PCL alone. Moreover, only PCL+MSC significantly reduces 18 F-fluorodeoxyglucose uptake on positron emission tomography. These findings suggest that adding MSCs promotes greater luminal expansion and potentially reduces the inflammatory process underlying NIH. The results demonstrate the utility of mechanical support loaded with MSCs at the outflow vein immediately after AVF formation to support maturation by minimizing NIH.


Assuntos
Fístula Arteriovenosa , Derivação Arteriovenosa Cirúrgica , Células-Tronco Mesenquimais , Insuficiência Renal Crônica , Ratos , Animais , Hiperplasia/patologia , Ratos Sprague-Dawley , Neointima/patologia , Implantes Absorvíveis , Tomografia Computadorizada por Raios X , Insuficiência Renal Crônica/terapia , Insuficiência Renal Crônica/patologia , Fístula Arteriovenosa/patologia , Células-Tronco Mesenquimais/patologia , Alicerces Teciduais
11.
Angiogenesis ; 26(4): 493-503, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37219736

RESUMO

BACKGROUND: Longitudinal mouse models of brain arteriovenous malformations (AVMs) are crucial for developing novel therapeutics and pathobiological mechanism discovery underlying brain AVM progression and rupture. The sustainability of existing mouse models is limited by ubiquitous Cre activation, which is associated with lethal hemorrhages resulting from AVM formation in visceral organs. To overcome this condition, we developed a novel experimental mouse model of hereditary hemorrhagic telangiectasia (HHT) with CreER-mediated specific, localized induction of brain AVMs. METHODS: Hydroxytamoxifen (4-OHT) was stereotactically delivered into the striatum, parietal cortex, or cerebellum of R26CreER; Alk12f/2f (Alk1-iKO) littermates. Mice were evaluated for vascular malformations with latex dye perfusion and 3D time-of-flight magnetic resonance angiography (MRA). Immunofluorescence and Prussian blue staining were performed for vascular lesion characterization. RESULTS: Our model produced two types of brain vascular malformations, including nidal AVMs (88%, 38/43) and arteriovenous fistulas (12%, 5/43), with an overall frequency of 73% (43/59). By performing stereotaxic injection of 4-OHT targeting different brain regions, Alk1-iKO mice developed vascular malformations in the striatum (73%, 22/30), in the parietal cortex (76%, 13/17), and in the cerebellum (67%, 8/12). Identical application of the stereotaxic injection protocol in reporter mice confirmed localized Cre activity near the injection site. The 4-week mortality was 3% (2/61). Seven mice were studied longitudinally for a mean (SD; range) duration of 7.2 (3; 2.3-9.5) months and demonstrated nidal stability on sequential MRA. The brain AVMs displayed microhemorrhages and diffuse immune cell invasion. CONCLUSIONS: We present the first HHT mouse model of brain AVMs that produces localized AVMs in the brain. The mouse lesions closely resemble the human lesions for complex nidal angioarchitecture, arteriovenous shunts, microhemorrhages, and inflammation. The model's longitudinal robustness is a powerful discovery resource to advance our pathomechanistic understanding of brain AVMs and identify novel therapeutic targets.


Assuntos
Fístula Arteriovenosa , Malformações Arteriovenosas , Telangiectasia Hemorrágica Hereditária , Animais , Camundongos , Humanos , Telangiectasia Hemorrágica Hereditária/patologia , Malformações Arteriovenosas/patologia , Fístula Arteriovenosa/patologia , Encéfalo/patologia
12.
Neurology ; 101(12): 524-535, 2023 09 19.
Artigo em Inglês | MEDLINE | ID: mdl-37185123

RESUMO

In this review, we describe the pathophysiology, diagnosis, and treatment of spinal dorsal intradural arteriovenous fistulas (DI-AVFs), focusing on novel research areas. DI-AVFs compose the most common subgroup of spinal arteriovenous lesions and most commonly involve the thoracic spine, followed by lumbar and sacral segments. The pathogenesis underlying DI-AVFs is an area of emerging understanding, thought to be attributable to venous congestion and hypertension that precipitate ascending myelopathy. Patients with DI-AVFs typically present with motor, sensory, or urinary dysfunction, although a wide swath of other less common symptoms has been reported. DI-AVFs can be subdivided by spinal region, which in turn is associated with 4 distinct clinical phenotypes: craniocervical junction (CCJ), subaxial cervical, thoracic, and lumbosacral. Patients with CCJ and lumbosacral DI-AVFs have particularly interesting presentations and treatment considerations. High-value diagnostic findings on MRI include flow voids, missing-piece sign, and T2-weighted intramedullary hyperintensity. However, digital subtraction angiography is the gold standard for diagnosis and localization of DI-AVFs and for definitive treatment planning. Surgical disconnection of DI-AVFs is almost universally curative and frontline treatment, especially for CCJ and lumbosacral DI-AVFs. Endovascular techniques evolve in promising ways, such as improved visualization, distal access, and liquid embolic techniques. The pathophysiology of DI-AVFs is better understood using newly identified radiologic diagnostic markers. Despite new techniques and devices introduced in the endovascular field, surgery remains the gold-standard treatment for DI-AVFs.


Assuntos
Fístula Arteriovenosa , Malformações Vasculares do Sistema Nervoso Central , Doenças da Medula Espinal , Humanos , Medula Espinal/patologia , Fístula Arteriovenosa/diagnóstico por imagem , Fístula Arteriovenosa/terapia , Fístula Arteriovenosa/patologia , Coluna Vertebral/patologia , Doenças da Medula Espinal/diagnóstico por imagem , Doenças da Medula Espinal/terapia , Imageamento por Ressonância Magnética , Malformações Vasculares do Sistema Nervoso Central/diagnóstico por imagem , Malformações Vasculares do Sistema Nervoso Central/terapia
13.
Int J Mol Sci ; 24(8)2023 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-37108733

RESUMO

Rates of arteriovenous fistula maturation failure are still high, especially when suboptimal size veins are used. During successful maturation, the vein undergoes lumen dilatation and medial thickening, adapting to the increased hemodynamic forces. The vascular extracellular matrix plays an important role in regulating these adaptive changes and may be a target for promoting fistula maturation. In this study, we tested whether a device-enabled photochemical treatment of the vein prior to fistula creation facilitates maturation. Sheep cephalic veins were treated using a balloon catheter coated by a photoactivatable molecule (10-8-10 Dimer) and carrying an internal light fiber. As a result of the photochemical reaction, new covalent bonds were created during light activation among oxidizable amino acids of the vein wall matrix proteins. The treated vein lumen diameter and media area became significantly larger than the contralateral control fistula vein at 1 week (p = 0.035 and p = 0.034, respectively). There was also a higher percentage of proliferating smooth muscle cells in the treated veins than in the control veins (p = 0.029), without noticeable intimal hyperplasia. To prepare for the clinical testing of this treatment, we performed balloon over-dilatation of isolated human veins and found that veins can tolerate up to 66% overstretch without notable histological damage.


Assuntos
Fístula Arteriovenosa , Derivação Arteriovenosa Cirúrgica , Humanos , Animais , Ovinos , Diálise Renal , Veias/patologia , Dilatação , Fístula Arteriovenosa/patologia , Resultado do Tratamento
14.
Int J Neurosci ; 133(5): 492-495, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-33931000

RESUMO

BACKGROUND:  In the literature, filum terminale arteriovenous shunts (FTAVSs) always feature a single shunt point. Nidus-type FTAVSs have rarely been reported, and the best treatment strategy is unclear. This is a report of one exceptional case of a nidus-type FTAVS and surgical treatment of the lesion. CASE DESCRIPTION: The patient suffered from cauda equina syndrome for 9 months. Magnetic resonance imaging and spinal angiography revealed a nidus-type FTAVF at the L2 level. Surgical resection was performed in the hybrid operating room, and the nidus was completely resected with the assistance of intraoperative methylene blue angiography and neurophysiological monitoring. The postoperative neurological function was stable. CONCLUSIONS: A nidus-type arteriovenous shunt could originate from the FT, and in such cases, complete surgical resection with intraoperative neurophysiological monitoring in a hybrid operating room should be suggested.


Assuntos
Fístula Arteriovenosa , Cauda Equina , Humanos , Cauda Equina/diagnóstico por imagem , Cauda Equina/cirurgia , Fístula Arteriovenosa/diagnóstico por imagem , Fístula Arteriovenosa/cirurgia , Fístula Arteriovenosa/patologia , Procedimentos Neurocirúrgicos/métodos , Imageamento por Ressonância Magnética , Angiografia Digital/métodos
15.
J Neurol ; 270(3): 1745-1753, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36534201

RESUMO

BACKGROUND: The purpose was to clarify diagnostic clues and pitfalls in cranio-cervical junction arteriovenous fistulas (CCJ AVFs) with congestive myelopathy. METHODS: In a multicenter observational study by the Neurospinal Society of Japan, we described the demographics, clinical courses, imaging findings, and outcomes of consecutive patients with CCJ AVFs presenting with congestive myelopathy between 2009 and 2019. RESULTS: Twenty-seven patients were included (mean age, 70 years; male, 96%). Progressive symptoms within one day to one month were more common (63%) than chronic symptoms. Myelopathic symptoms were characterized by ascending paralysis beginning from the legs, involving the trunk and arms, and sometimes ending in the brainstem. Fifteen patients (56%) received a misdiagnosis, including acute transverse myelitis. The most common MRI findings were venous congestive edema of the cervical cord (96%) and the brainstem (63%) and surrounding vascular flow voids (100%). The mean extension of congestive edema was 5.5 ± 2.9 vertebral segments. The most common angiographic findings were a dural AVF (78%) at the C1 level (81%) with descending venous drainage (85%). Seven patients (26%) were administered steroids, which resulted in neurological decline in 3. Neurosurgical obliteration of the AVF led to improvements in MRI findings in 75% and a functional status in 67%; however, 44% remained dependent. CONCLUSIONS: The myelopathy of CCJ AVFs was characterized by acute ascending paralysis in elderly men. A misdiagnosis was common because of the acute presentation due to a longitudinally extensive spinal cord lesion. Dilated vessels on MRI were a key finding for the correct diagnosis. What is already known on this topic? Slowly progressive myelopathy is a well-known symptom that results from impaired spinal venous drainage due to thoracolumbar AVFs. Although cranio-cervical junction arteriovenous fistulas (CCJ AVFs) constitute a treatable cause of congestive myelopathy, detailed information is not currently available due to their rarity. What does this study add? CCJ AVFs often presented with acute ascending myelopathy in elderly men due to a longitudinally extending cervical cord lesion with surrounding flow voids. Steroid pulse therapy was not effective or even harmful to congestive myelopathy, while neurosurgical treatment effectively obliterated AVFs. How might this study affect research, practice or policy? The results obtained revealed diagnostic clues and pitfalls from the largest dataset of patients with CCJ AVFs in a multicenter cohort.


Assuntos
Fístula Arteriovenosa , Malformações Vasculares do Sistema Nervoso Central , Mielite Transversa , Doenças da Medula Espinal , Humanos , Masculino , Idoso , Mielite Transversa/diagnóstico , Mielite Transversa/diagnóstico por imagem , Fístula Arteriovenosa/patologia , Fístula Arteriovenosa/cirurgia , Doenças da Medula Espinal/diagnóstico por imagem , Doenças da Medula Espinal/cirurgia , Imageamento por Ressonância Magnética , Paralisia , Medula Espinal/diagnóstico por imagem , Medula Espinal/patologia , Malformações Vasculares do Sistema Nervoso Central/diagnóstico , Malformações Vasculares do Sistema Nervoso Central/diagnóstico por imagem
17.
Spinal Cord Ser Cases ; 8(1): 78, 2022 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-36050309

RESUMO

INTRODUCTION: Neurofibromatosis type 1 (NF-1) is an autosomal-dominant disorder affecting 1 in 3000 individuals worldwide. NF-1 is characterized by café-au-lait macules and peripheral nerve sheath tumors. Patients with NF-1 frequently exhibit bony dysplasia, including spinal deformities such as scoliosis or kyphosis, pseudarthrosis of the tibia, and soft tissue tumors. Some patients with NF-1 exhibit spinal changes, including acutely angled cervical kyphosis. Prior studies have also described arteriovenous (AV) fistulas in individuals with NF-1, as well as a predisposition to cervical fistulas which display symptoms secondary to mass effect, rather than hemorrhage. Sometimes, fistulas are incidentally detected during evaluations for cervical kyphotic deformities. CASE PRESENTATION: The case herein describes a patient with NF-1 who exhibited a severe cervical spinal kyphotic deformity and a vertebral AV fistula. The patient initially presented with neck pain that radiated to all four limbs and resulted in limb weakness. DISCUSSION: Spinal kyphosis is common in patients with NF-1, and if dystrophic changes are noted on plain radiographs, MRI should be considered for the further survey of potential spinal vascular lesions.


Assuntos
Fístula Arteriovenosa , Cifose , Neurofibromatose 1 , Fístula Arteriovenosa/complicações , Fístula Arteriovenosa/diagnóstico por imagem , Fístula Arteriovenosa/patologia , Vértebras Cervicais/diagnóstico por imagem , Vértebras Cervicais/patologia , Humanos , Cifose/complicações , Cifose/diagnóstico por imagem , Neurofibromatose 1/complicações , Neurofibromatose 1/diagnóstico , Neurofibromatose 1/patologia , Quadriplegia/complicações , Quadriplegia/etiologia
18.
Cardiovasc Ther ; 2022: 7576388, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35812724

RESUMO

Purpose: An arteriovenous fistula (AVF) is the preferred vascular access mode for maintenance hemodialysis, and access stenosis and thrombosis are the primary causes of AVF dysfunction. This study is aimed at exploring the molecular mechanisms underlying AVF development and the roles of the heme oxygenase 1/peroxisome proliferator-activated receptor gamma (HO-1/PPAR-γ) pathway in AVF. Method: AVF model mice were established, and the vascular tissues from the arteriovenous anastomosis site were sent for mRNA sequencing. Differentially expressed mRNAs (DEmRNAs) were screened and subjected to functional analysis. Thereafter, the mice with HO-1 knockdown and coprotoporphyrin IX chloride (COPP) pretreatment were used to investigate the roles of the HO-1/PPAR-γ pathway in AVF. Results: By sequencing, 2514 DEmRNAs, including 1323 upregulated and 1191 downregulated genes, were identified. These DEmRNAs were significantly enriched in the PPAR signaling pathway, AMPK signaling pathway, glucagon signaling pathway, IL-17 signaling pathway, and Toll-like receptor signaling pathway. High expression of HO-1 and PPAR-γ reduced endothelial damage and intimal hyperplasia during AVF maturation. After AVF was established, the levels of transforming growth factor-ß (TGF-ß), interleukin-1ß (IL-1ß), interleukin-18 (IL-18), and reactive oxygen species (ROS) were significantly increased (P < 0.05), and HO-1 normal expression and COPP pretreatment evidently decreased their levels in AVF (P < 0.05). Additionally, AVF significantly upregulated HO-1 and PPAR-γ and downregulated MMP9, and COPP pretreatment and HO-1 normal expression further upregulated and downregulated their expression. Conclusion: The HO-1/PPAR-γ pathway may suppress intimal hyperplasia induced by AVF and protect the intima of blood vessels by regulating MMP9 and ROS, thus mitigating AVF dysfunction.


Assuntos
Fístula Arteriovenosa , Heme Oxigenase-1 , Proteínas de Membrana , Estresse Oxidativo , PPAR gama , Animais , Fístula Arteriovenosa/patologia , Citocinas/análise , Técnicas de Silenciamento de Genes , Heme Oxigenase-1/metabolismo , Hiperplasia/prevenção & controle , Inflamação , Masculino , Metaloproteinase 9 da Matriz/metabolismo , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , PPAR gama/metabolismo , RNA Mensageiro , Espécies Reativas de Oxigênio/análise , Transdução de Sinais
19.
Neurosurg Focus ; 53(1): E12, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35901717

RESUMO

OBJECTIVE: This study aimed to explore whether intervention can benefit Spetzler-Martin (SM) grade IV-V arteriovenous malformations (AVMs). METHODS: Eighty-two patients with SM grade IV-V AVMs were retrospectively reviewed from 2015 to 2018. Patients were divided into two groups: those who received conservative management (22 cases [26.8%]) and intervention (60 cases [73.2%], including 21 cases of microsurgery, 19 embolization, and 20 hybrid surgery). Neurofunctional outcomes were assessed with the modified Rankin Scale (mRS). The primary outcome was long-term neurofunctional status, and the secondary outcomes were short-term neurofunctional status, long-term obliteration rate, seizure control, and risk of subsequent hemorrhage. RESULTS: Regarding the primary outcome, after an average of 4.7 years of clinical follow-up, long-term neurofunctional outcomes were similar after conservative management or intervention (absolute difference -0.4 [95% CI -1.5 to 0.7], OR 0.709 [95% CI 0.461-1.090], p = 0.106), whereas intervention had an advantage over conservative management for avoidance of severe disability (defined as mRS score > 3) (1.7% vs 18.2%, absolute difference 16.5% [95% CI -23.6% to 56.6%], OR 0.076 [95% CI 0.008-0.727], p = 0.025). Regarding the secondary outcomes, intervention was conducive to better seizure control (Engel class I-II) (70.0% vs 0.0%, absolute difference 70.0% [95% CI 8.6%-131.4%], p = 0.010) and avoidance of subsequent hemorrhage (1.4% vs 6.0%, absolute difference 4.6% [95% CI -0.4% to 9.6%], p = 0.030). In the subgroup analysis based on different intervention modalities, microsurgery and hybrid surgery achieved higher complete obliteration rates than embolization (p < 0.001), and hybrid surgery resulted in significantly less intraoperative blood loss than microsurgery (p = 0.041). CONCLUSIONS: Intervention is reasonable for properly indicated SM grade IV-V AVMs because it provides satisfactory seizure control with decreased risks of severe disability and subsequent hemorrhage than conservative management. Clinical trial registration no.: NCT04572568 (ClinicalTrials.gov).


Assuntos
Fístula Arteriovenosa , Malformações Arteriovenosas Intracranianas , Procedimentos Cirúrgicos Operatórios , Fístula Arteriovenosa/patologia , Fístula Arteriovenosa/cirurgia , Perda Sanguínea Cirúrgica/prevenção & controle , Embolização Terapêutica , Humanos , Malformações Arteriovenosas Intracranianas/patologia , Malformações Arteriovenosas Intracranianas/cirurgia , Microcirurgia , Estudos Retrospectivos , Convulsões/prevenção & controle , Procedimentos Cirúrgicos Operatórios/métodos , Resultado do Tratamento
20.
J Vasc Interv Radiol ; 33(8): 904-912.e1, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35605817

RESUMO

PURPOSE: To assess venous wall vascularization and its correlation with neointimal hyperplasia (NIH) in failed arteriovenous fistulae (AVFs). MATERIALS AND METHODS: A total of 43 uremic patients who underwent de novo AVF creation and 39 patients who underwent reconstruction of failed fistulae were enrolled in the study. A 5-10-mm vein segment adjacent to the future fistula creation or reconstruction site was surgically removed and assessed using histopathological analyses and stained by immunohistochemistry to quantify vasa vasorum density (VVD). RESULTS: Both the intimal thickness (70.68 [28.81-99.54] vs 4.53 [2.69-7.30] µm, P < .001) and the intimal thickness-to-medial thickness ratio (2.20 [0.77-4.36] vs 0.15 [0.10-0.30], P < .001) were higher in failed AVFs than in preaccess veins. CD31- and factor VIII-marked VVDs in both the intima (6.31 [1.62-12.53] vs 0.0 [0.0-0.0], P < .001; 7.82 [3.33-11.61] vs 0.0 [0.0-0.0], P < .001) and media (10.0 [7.59-12.95] vs 3.71 [2.44-4.87], P < .001; 8.33 [5.55-13.0] vs 3.57 [2.53-4.82], P < .001) as well as the intimal VVD:medial VVD ratio (0.67 [0.19-1.08] vs 0.0 [0.0-0.0], P < .001; 0.71 [0.39-1.14] vs 0.0 [0.0-0.0], P < .001) were significantly higher in failed AVFs than in preaccess veins. Moreover, there was a positive relationship between the intimal VVD:medial VVD ratio and the intimal thickness:medial thickness ratio (P < .001). In addition, the vascular endothelial cell growth factor A expression was higher in failed AVFs than in preaccess veins. CONCLUSIONS: Vascularization of the vessel wall was noticeably more developed in the arterialized veins, especially at the NIH regions in failed AVFs.


Assuntos
Fístula Arteriovenosa , Derivação Arteriovenosa Cirúrgica , Falência Renal Crônica , Fístula Arteriovenosa/patologia , Derivação Arteriovenosa Cirúrgica/efeitos adversos , Humanos , Hiperplasia/patologia , Neointima/patologia , Diálise Renal , Veias/diagnóstico por imagem , Veias/patologia , Veias/cirurgia
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