scholarly journals Pathophysiology of Vascular Stenosis and Remodeling in Moyamoya Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Brandon M. Fox ◽  
Kirsten B. Dorschel ◽  
Michael T. Lawton ◽  
John E. Wanebo
Keyword(s):  
Moyamoya Disease ◽  
Cellular Proliferation ◽  
Vascular Inflammation ◽  
Neointimal Hyperplasia ◽  
Arterial Stenosis ◽  
Molecular Pathways ◽  
Matrix Remodeling ◽  
Vascular Networks ◽  
Internal Elastic Lamina ◽  
And Migration

Moyamoya disease (MMD) and moyamoya syndrome (MMS) are progressive vascular pathologies unique to the cerebrovasculature that are important causes of stroke in both children and adults. The natural history of MMD is characterized by primary progressive stenosis of the supraclinoid internal carotid artery, followed by the formation of fragile collateral vascular networks. In MMS, stenosis and collateralization occur in patients with an associated disease or condition. The pathological features of the stenosis associated with MMD include neointimal hyperplasia, disruption of the internal elastic lamina, and medial attenuation, which ultimately lead to progressive decreases in both luminal and external arterial diameter. Several molecular pathways have been implicated in the pathophysiology of stenosis in MMD with functions in cellular proliferation and migration, extracellular matrix remodeling, apoptosis, and vascular inflammation. Importantly, several of these molecular pathways overlap with those known to contribute to diseases of systemic arterial stenosis, such as atherosclerosis and fibromuscular dysplasia (FMD). Despite these possible shared mechanisms of stenosis, the contrast of MMD with other stenotic pathologies highlights the central questions underlying its pathogenesis. These questions include why the stenosis that is associated with MMD occurs in such a specific and limited anatomic location and what process initiates this stenosis. Further investigation of these questions is critical to developing an understanding of MMD that may lead to disease-modifying medical therapies. This review may be of interest to scientists, neurosurgeons, and neurologists involved in both moyamoya research and treatment and provides a review of pathophysiologic processes relevant to diseases of arterial stenosis on a broader scale.

The effects of oxidative stress on the development of atherosclerosis

2019 ◽  
Vol 400 (6) ◽  
pp. 711-732 ◽  
Author(s):  
Mohsen Khosravi ◽  
Adeleh Poursaleh ◽  
Ghasem Ghasempour ◽  
Shaikhnia Farhad ◽  
Mohammad Najafi
Keyword(s):  
Oxidative Stress ◽  
Cellular Proliferation ◽  
Nadh Oxidase ◽  
Macrophage Polarization ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Oxidative Modification ◽  
Oxidative Enzymes ◽  
Matrix Remodeling ◽  
And Migration

Abstract Atherosclerosis is a cardiovascular disease (CVD) known widely world wide. Several hypothesizes are suggested to be involved in the narrowing of arteries during process of atherogenesis. The oxidative modification hypothesis is related to oxidative and anti-oxidative imbalance and is the most investigated. The aim of this study was to review the role of oxidative stress in atherosclerosis. Furthermore, it describes the roles of oxidative/anti-oxidative enzymes and compounds in the macromolecular and lipoprotein modifications and in triggering inflammatory events. The reactive oxygen (ROS) and reactive nitrogen species (RNS) are the most important endogenous sources produced by non-enzymatic and enzymatic [myeloperoxidase (MPO), nicotinamide adenine dinucleotide phosphate (NADH) oxidase and lipoxygenase (LO)] reactions that may be balanced with anti-oxidative compounds [glutathione (GSH), polyphenols and vitamins] and enzymes [glutathione peroxidase (Gpx), peroxiredoxins (Prdx), superoxide dismutase (SOD) and paraoxonase (PON)]. However, the oxidative and anti-oxidative imbalance causes the involvement of cellular proliferation and migration signaling pathways and macrophage polarization leads to the formation of atherogenic plaques. On the other hand, the immune occurrences and the changes in extra cellular matrix remodeling can develop atherosclerosis process.

Wnt/beta-catenin and PI3K/Akt/mTOR Signaling Pathways in Glioblastoma: Two Main Targets for Drug Design: A Review

2020 ◽  
Vol 26 (15) ◽  
pp. 1729-1741 ◽  
Author(s):  
Seyed H. Shahcheraghi ◽  
Venant Tchokonte-Nana ◽  
Marzieh Lotfi ◽  
Malihe Lotfi ◽  
Ahmad Ghorbani ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Molecular Mechanisms ◽  
Cellular Proliferation ◽  
Chemotherapy Resistance ◽  
Wnt Signaling Pathway ◽  
Therapeutic Interventions ◽  
Beta Catenin ◽  
Clinical Prognosis ◽  
Invasion And Migration ◽  
And Migration

: Glioblastoma (GBM) is the most common and malignant astrocytic glioma, accounting for about 90% of all brain tumors with poor prognosis. Despite recent advances in understanding molecular mechanisms of oncogenesis and the improved neuroimaging technologies, surgery, and adjuvant treatments, the clinical prognosis of patients with GBM remains persistently unfavorable. The signaling pathways and the regulation of growth factors of glioblastoma cells are very abnormal. The various signaling pathways have been suggested to be involved in cellular proliferation, invasion, and glioma metastasis. The Wnt signaling pathway with its pleiotropic functions in neurogenesis and stem cell proliferation is implicated in various human cancers, including glioma. In addition, the PI3K/Akt/mTOR pathway is closely related to growth, metabolism, survival, angiogenesis, autophagy, and chemotherapy resistance of GBM. Understanding the mechanisms of GBM’s invasion, represented by invasion and migration, is an important tool in designing effective therapeutic interventions. This review will investigate two main signaling pathways in GBM: PI3K/Akt/mTOR and Wnt/beta-catenin signaling pathways.

Pathology and Pathobiology of Pulmonary Hypertension

2017 ◽  
Vol 38 (05) ◽  
pp. 571-584 ◽  
Author(s):  
Peter Dorfmüller ◽  
Christophe Guignabert
Keyword(s):  
Pulmonary Hypertension ◽  
Vascular Inflammation ◽  
Right Heart Catheterization ◽  
Point Of View ◽  
Heart Catheterization ◽  
Pulmonary Endothelium ◽  
Hemodynamic State ◽  
Pulmonary Arterial ◽  
Genetic And Environmental Factors ◽  
And Migration

Pulmonary hypertension (PH) is a hemodynamic state defined by a mean pulmonary artery pressure ≥ 25 mm Hg during resting right heart catheterization. PH can result from precapillary (arterial) or postcapillary (venous) pathophysiological mechanisms. Interestingly, recent PH pathology has shown that pulmonary arterial or pulmonary venous remodelling are rarely independent phenomena, but frequently occur in combined fashion in lungs from patients suffering from different forms of PH, including pulmonary arterial hypertension (PAH). In PAH, it is now becoming clear that aberrant signals present in vessel wall microenvironment, which is largely orchestrated by dysfunctional pulmonary endothelial cells, are key contributors of the pulmonary vascular remodeling process, fostering proliferation, and survival and migration of resident pulmonary vascular cells such as smooth muscle cells, myofibroblasts, and pericytes. In addition, both genetic and environmental factors are also critical in the development of pulmonary vascular inflammation and chronic impairment of the pulmonary endothelium. This article outlines the current understanding of this disease from the point of view of pathology and pathobiology.

Abstract 15984: Rpl13a Small Nucleolar RNAs Promote Oxidative Stress and Atherosclerosis

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Lisheng Zhang ◽  
Jiaohui Wu ◽  
Andrew J Vista ◽  
Leigh Brian ◽  
Yushi Bai ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Carotid Arteries ◽  
Neointimal Hyperplasia ◽  
Foam Cells ◽  
Slice Thickness ◽  
Small Nucleolar Rnas ◽  
And Migration ◽  
Nucleolar Rnas ◽  
Proliferation And Migration

Reactive oxygen species (ROS) contribute to atherogenesis. An unusual mechanism that increases cellular ROS levels and oxidative stress involves 4 ubiquitously expressed noncoding small nucleolar RNAs (snoRNAs) from introns of the ribosomal protein L13a ( Rpl13a ) locus: U32a , U33 , U34 , and U35a . We tested the hypothesis that these snoRNAs promote aortic smooth muscle cell (SMC) activation and vascular inflammation, by using “snoKO” mice with targeted deletion of the 4 snoRNAs (but not Rpl13a ). Compared with congenic WT SMCs, snoKO SMCs showed 40±20% lower ROS levels, assessed by DCF fluorescence ( p <0.02). Congruently, ROS levels were 35±5% lower in snoKO than WT aorta and carotid frozen sections ( p <0.01), assessed by CellROX Orange fluorescence. Proliferation and migration evoked by FBS and PDGF-BB, respectively, were each 30±10% less in snoKO than WT SMCs ( p <0.01 for each). To assess SMC migration and proliferation in vivo, we performed carotid artery endothelial denudation. Before injury, snoKO and WT carotid arteries were morphologically equivalent. Four wk after injury, carotid neointimal hyperplasia was 57±9% less and luminal area was 40±20 % more in snoKO than in WT mice ( p <0.01). WT and snoKO mice had equivalent heart rates and systolic blood pressures by tail-cuff plethysmography: 480±20 vs 420±80 beats/min; 133±5, 132±7 mm Hg, respectively (n=5/group). To test whether snoRNAs affect atherosclerosis, we orthotopically transplanted carotid arteries from WT and snoKO mice into congenic Apoe -/- mice. Six wk post-op, atherosclerotic neointima was 70±10% smaller in snoKO than in WT carotids ( p <0.01). To assess SMC-to-foam-cell transdifferentiation, which is ROS-dependent, carotid cross-sections were stained for apoE to identify graft-derived cells and for cholesteryl ester with BODIPY. BODIPY + foam cells comprised 21±3% and 11±7% of neointimal area in WT and snoKO carotids, respectively ( p <0.05). Confocal co-localization of apoE and BODIPY (optical slice thickness 1 μm) showed that graft-derived foam cells were 2.0±0.6-fold more prevalent in WT than in snoKO carotids ( p <0.01). We conclude that Rpl13a snoRNAs promote SMC ROS levels, proliferation and migration in vitro and in vivo, and that these snoRNAs augment atherosclerosis.

scholarly journals AC016745.3 Regulates the Transcription of AR Target Genes by Antagonizing NONO

Life ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 1208
Author(s):  
Yali Lu ◽  
Xuechao Wan ◽  
Wenhua Huang ◽  
Lu Zhang ◽  
Jun Luo ◽  
...  
Keyword(s):  
Transcriptional Activity ◽  
Target Genes ◽  
Cellular Proliferation ◽  
Mechanisms Of Action ◽  
Adenocarcinoma Cell Line ◽  
Specific Mechanism ◽  
Rna Immunoprecipitation ◽  
Non Coding Rnas ◽  
And Migration ◽  
Proliferation And Migration

The androgen receptor (AR) and its related signaling pathways play an important role in the development of prostate cancer (PCa). Long non-coding RNAs (lncRNAs) are involved in the regulation of tumorigenesis and development, but their specific mechanism of action remains unclear. This study examines the function and mechanisms of action of lncRNA AC016745.3 in the development of PCa. It shows that dihydrotestosterone (DHT) results in the AR-dependent suppression of AC016745.3 expression in the LNCaP androgen-sensitive human prostate adenocarcinoma cell line. In addition, overexpression of AC016745.3 inhibits the proliferation and migration of PCa cells, and suppresses the expression of AR target genes. This research also demonstrates that the protein NONO interacts with AR and functions as an AR co-activator, promoting AR transcriptional activity. Furthermore, using RNA immunoprecipitation (RIP)-PCR experiments, the study demonstrates that both NONO and AR can bind AC016745.3. Moreover, cell phenotypic experiments reveal that NONO can promote cellular proliferation and migration, and that AC016745.3 can partially antagonize the pro-oncogenic functions of NONO in PCa cells. In summary, the results indicate that AC016745.3 can bind NONO, suppressing its ability to promote AR-dependent transcriptional activity. Furthermore, DHT-dependent suppression of AC016745.3 expression can enhance NONO’s promotion effect on AR.

scholarly journals A case report of moyamoya disease in children treated with encephalo-duro-myo-arterio-pericranial synangiosis

2021 ◽  
Author(s):  
Julius July
Keyword(s):  
Computed Tomography ◽  
Case Report ◽  
Magnetic Resonance Angiography ◽  
Moyamoya Disease ◽  
Internal Carotid ◽  
Language Function ◽  
Vascular Networks ◽  
Ischemic Event ◽  
Special Challenge ◽  
Ischemic Attack

Moyamoya disease that manifests during childhood may pose a special challenge for surgeons. We report a case of a 10-year-old girl who suffered from moyamoya disease and was successfully treated with encephalo-duro-myo-arterio-pericranial synangiosis (EDMAPS). She presented with a recurrent transient ischemic attack that worsened for 1 year. She was aphasic globally (sensory and motor) and had slightly weak right extremities. Her magnetic resonance angiography and computed tomography angiography showed the typical features of moyamoya disease with bilateral stenosis at the terminal internal carotid artery, bilaterally abnormal vascular networks, and a left ischemic event involving the temporoparietal region. She was recovered well after underwent bilateral EDMAPS, fully regained her language function after 3 months, and gathered her strength back. Therefore, EDMAPS could be a good, safe, and effective treatment for moyamoya disease in children.

scholarly journals Transcriptional profiling of the murine airway response to acute ozone exposure

2019 ◽  
Author(s):  
Adelaide Tovar ◽  
Gregory J. Smith ◽  
Joseph M. Thomas ◽  
Jack R. Harkema ◽  
Samir N. P. Kelada
Keyword(s):  
Gene Expression ◽  
Airway Inflammation ◽  
Cellular Proliferation ◽  
Expression Patterns ◽  
Differentially Expressed ◽  
Ozone Exposure ◽  
Matrix Remodeling ◽  
Transcriptional Responses ◽  
Morphological Alterations ◽  
Cell Counts

AbstractExposure to ambient ozone (O3) pollution causes airway inflammation, epithelial injury, and decreased lung function. Long-term exposure is associated with increased mortality and exacerbations of respiratory conditions. While the adverse health effects of O3 exposure have been thoroughly described, less is known about the molecular processes that drive these outcomes. The aim of this study was to describe the cellular and molecular alterations observed in murine airways after exposure to either 1 or 2 ppm O3. After exposing adult, female C57BL/6J mice to filtered air, 1 or 2 ppm O3 for 3 hours, we assessed hallmark responses including airway inflammatory cell counts, epithelial permeability, cytokine secretion, and morphological alterations of the large airways. Further, we performed RNA-seq to profile gene expression in two critical tissues involved in O3 responses: conducting airways (CA) and airway macrophages (AM). We observed a concentration-dependent increase in airway inflammation and injury, and a large number of genes were differentially expressed in both target tissues at both concentrations of O3. Genes that were differentially expressed in CA were generally associated with barrier function, detoxification processes, and cellular proliferation. The differentially expressed genes in AM were associated with innate immune signaling, cytokine production, and extracellular matrix remodeling. Overall, our study has described transcriptional responses to acute O3 exposure, revealing both shared and unique gene expression patterns across multiple concentrations of O3 and in two important O3-responsive tissues. These profiles provide broad mechanistic insight into pulmonary O3 toxicity, and reveal a variety of targets for refined follow-up studies.

scholarly journals A neutralizing IL-11 antibody reduces vessel hyperplasia in a mouse carotid artery wire injury model

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
David Schumacher ◽  
Elisa A. Liehn ◽  
Pakhwan Nilcham ◽  
David Castaño Mayan ◽  
Chutima Rattanasopa ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Wall Thickness ◽  
Vessel Wall ◽  
Neointimal Hyperplasia ◽  
Endothelial Injury ◽  
Collagen Content ◽  
Arterial Stenosis ◽  
Matrix Metalloproteinase 2 ◽  
Vessel Wall Thickness ◽  
Artery Disease

AbstractVascular restenosis remains a major problem in patients with coronary artery disease (CAD) and peripheral artery disease (PAD). Neointimal hyperplasia, defined by post-procedure proliferation and migration of vascular smooth muscle cells (VSMCs) is a key underlying pathology. Here we investigated the role of Interleukin 11 (IL-11) in a mouse model of injury-related plaque development. Apoe−/− mice were fed a hyperlipidaemic diet and subjected to carotid wire injury of the right carotid. Mice were injected with an anti-IL11 antibody (X203), IgG control antibody or buffer. We performed ultrasound analysis to assess vessel wall thickness and blood velocity. Using histology and immunofluorescence approaches, we determined the effects of IL-11 inhibition on VSMC and macrophages phenotypes and fibrosis. Treatment of mice with carotid wire injury using X203 significantly reduced post-endothelial injury vessel wall thickness, and injury-related plaque, when compared to control. Immunofluorescence staining of the injury-related plaque showed that X203 treatment did not reduce macrophage numbers, but reduced the number of VSMCs and lowered matrix metalloproteinase 2 (MMP2) levels and collagen content in comparison to control. X203 treatment was associated with a significant increase in smooth muscle protein 22α (SM22α) positive cells in injury-related plaque compared to control, suggesting preservation of the contractile VSMC phenotype. Interestingly, X203 also reduced the collagen content of uninjured carotid arteries as compared to IgG, showing an additional effect on hyperlipidemia-induced arterial remodeling in the absence of mechanical injury. Therapeutic inhibition of IL-11 reduced vessel wall thickness, attenuated neointimal hyperplasia, and has favorable effects on vascular remodeling following wire-induced endothelial injury. This suggests IL-11 inhibition as a potential novel therapeutic approach to reduce arterial stenosis following revascularization in CAD and PAD patients.

scholarly journals Jujuboside B Inhibits Neointimal Hyperplasia and Prevents Vascular Smooth Muscle Cell Dedifferentiation, Proliferation, and Migration via Activation of AMPK/PPAR-γ Signaling

2021 ◽  
Vol 12 ◽  
Author(s):  
Zaixiong Ji ◽  
Jiaqi Li ◽  
Jianbo Wang
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Neointimal Hyperplasia ◽  
Muscle Cells ◽  
Cell Dedifferentiation ◽  
Ppar Γ ◽  
And Migration ◽  
Proliferation And Migration

The uncontrolled proliferation and migration of vascular smooth muscle cells is a critical step in the pathological process of restenosis caused by vascular intimal hyperplasia. Jujuboside B (JB) is one of the main biologically active ingredients extracted from the seeds of Zizyphus jujuba (SZJ), which has the properties of anti-platelet aggregation and reducing vascular tension. However, its effects on restenosis after vascular intervention caused by VSMCs proliferation and migration remain still unknown. Herein, we present novel data showing that JB treatment could significantly reduce the neointimal hyperplasia of balloon-damaged blood vessels in Sprague-Dawley (SD) rats. In cultured VSMCs, JB pretreatment significantly reduced cell dedifferentiation, proliferation, and migration induced by platelet-derived growth factor-BB (PDGF-BB). JB attenuated autophagy and reactive oxygen species (ROS) production stimulated by PDGF-BB. Besides, JB promoted the phosphorylation of adenosine monophosphate-activated protein kinase (AMPK) and the expression of peroxisome proliferator-activated receptor-γ (PPAR-γ). Notably, inhibition of AMPK and PPAR-γ partially reversed the ability of JB to resist the proliferation and migration of VSMCs. Taken as a whole, our findings reveal for the first time the anti-restenosis properties of JB in vivo and in vitro after the endovascular intervention. JB antagonizes PDGF-BB-induced phenotypic switch, proliferation, and migration of vascular smooth muscle cells partly through AMPK/PPAR-γ pathway. These results indicate that JB might be a promising clinical candidate drug against in-stent restenosis, which provides a reference for further research on the prevention and treatment of vascular-related diseases.

scholarly journals PIMREG expression level predicts glioblastoma patient survival and affects temozolomide resistance and DNA damage response

2021 ◽  
Author(s):  
Rodolfo Bortolozo Serafim ◽  
Cibele Cardoso ◽  
Vanessa Arfelli ◽  
Valeria Valente ◽  
Leticia Fröhlich Archangelo
Keyword(s):  
Dna Damage ◽  
Nervous System ◽  
Dna Damage Response ◽  
Cellular Proliferation ◽  
Patient Survival ◽  
Glioblastoma Cells ◽  
Damage Response ◽  
Genotoxic Agents ◽  
And Migration ◽  
And Function

Abstract PIMREG expression strongly correlates with cellular proliferation in both malignant and normal cells. Throughout embryo development, PIMREG expression is prominent at the central nervous system. Recent studies have described high levels of PIMREG transcripts in different types of tumors and correlated with patient survival and tumor aggressiveness. Given the emerging significance of PIMREG in carcinogenesis and its putative role in the context of the nervous system, we investigated the expression and function of PIMREG in gliomas, the most common primary brain tumors. We performed an extensive analysis of PIMREG expression in tumors samples of glioma patients, assessed the effects of PIMREG silencing and overexpression on the sensitivity of glioblastoma cell lines treated with genotoxic agents commonly used for treating patients and assessed for treatment response, proliferation and migration. We show that glioblastoma exhibits the highest levels of PIMREG expression among all cancers analyzed and that elevated PIMREG expression is a biomarker for glioma progression and patient outcome. Moreover, PIMREG is induced by genotoxic agents and its silencing renders glioblastoma cells sensitive to temozolomide treatment and affects ATR- and ATM-dependent signaling. Our data demonstrate that PIMREG plays a role in DNA damage response and temozolomide resistance of glioblastoma cells and further support the PIMREG role in tumorigenesis.

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