Vascular CellPub Date : 2013-01-14DOI: 10.1186/2045-824X-5-1
Dileep Sharma, Saso Ivanovski, Mark Slevin, Stephen Hamlet, Tudor S Pop, Klara Brinzaniuc, Eugen B Petcu, Rodica I Miroiu
{"title":"Bisphosphonate-related osteonecrosis of jaw (BRONJ): diagnostic criteria and possible pathogenic mechanisms of an unexpected anti-angiogenic side effect.","authors":"Dileep Sharma, Saso Ivanovski, Mark Slevin, Stephen Hamlet, Tudor S Pop, Klara Brinzaniuc, Eugen B Petcu, Rodica I Miroiu","doi":"10.1186/2045-824X-5-1","DOIUrl":"https://doi.org/10.1186/2045-824X-5-1","url":null,"abstract":"<p><p>Recently, bisphosphonates (BPs) have been widely used in medical practice as anti-resorptive agents owing to their anti-osteoclatic action. In addition, these compounds are also used for their analgesic action and their potential anti-tumour effect. Patients treated with BPs may subsequently develop osteonecrosis of the jaw or maxillary bone after minor local trauma including dental work, recently labelled as bisphosphonate osteonecrosis of jaw (BRONJ). However, the etiopathogenic mechanisms of this pathological condition are poorly understood. Although, several pathways have been proposed for BRONJ occurrence, no single model can explain all morphological changes observed at the macro- and microscopic level. Recent research suggests that BPs may promote an anti-angiogenic effect which contributes directly to the clinical features associated with BRONJ. Remarkably, the anti-angiogenic effect promoting BRONJ might be in keeping with the anti-neoplastic action of BPs. The current review, presents clinical diagnostic criteria. In addition, based on our own experience we describe the histopathological criteria for diagnosis of BRONJ and the possible pathways which may lead to this frustrating pathological condition.</p>","PeriodicalId":23948,"journal":{"name":"Vascular Cell","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2013-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/2045-824X-5-1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31159706","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Vascular CellPub Date : 2012-12-24DOI: 10.1186/2045-824X-4-21
Charalampos Birmpas, Jean Paul Briand, Josẻ Courty, Panagiotis Katsoris
{"title":"The pseudopeptide HB-19 binds to cell surface nucleolin and inhibits angiogenesis.","authors":"Charalampos Birmpas, Jean Paul Briand, Josẻ Courty, Panagiotis Katsoris","doi":"10.1186/2045-824X-4-21","DOIUrl":"https://doi.org/10.1186/2045-824X-4-21","url":null,"abstract":"<p><strong>Background: </strong>Nucleolin is a protein over-expressed on the surface of tumor and endothelial cells. Recent studies have underlined the involvement of cell surface nucleolin in tumor growth and angiogenesis. This cell surface molecule serves as a receptor for various ligands implicated in pathophysiological processes such as growth factors, cell adhesion molecules like integrins, selectins or laminin-1, lipoproteins and viruses (HIV and coxsackie B). HB-19 is a synthetic multimeric pseudopeptide that binds cell surface expressed nucleolin and inhibits both tumor growth and angiogenesis.</p><p><strong>Methodology/principal findings: </strong>In the present work, we further investigated the biological actions of pseudopeptide HB-19 on HUVECs. In a previous work, we have shown that HB-19 inhibits the in vivo angiogenesis on the chicken embryo CAM assay. We now provide evidence that HB-19 inhibits the in vitro adhesion, migration and proliferation of HUVECs without inducing their apoptosis. The above biological actions seem to be regulated by SRC, ERK1/2, AKT and FAK kinases as we found that HB-19 inhibits their activation in HUVECs. Matrix metalloproteinases (MMPs) play crucial roles in tumor growth and angiogenesis, so we investigated the effect of HB-19 on the expression of MMP-2 and we found that HB-19 downregulates MMP-2 in HUVECs. Finally, down regulation of nucleolin using siRNA confirmed the implication of nucleolin in the biological actions of these peptides.</p><p><strong>Conclusions/significance: </strong>Taken together, these results indicate that HB-19 could constitute an interesting tool for tumor therapy strategy, targeting cell surface nucleolin.</p>","PeriodicalId":23948,"journal":{"name":"Vascular Cell","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2012-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/2045-824X-4-21","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31144539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Vascular CellPub Date : 2012-12-10DOI: 10.1186/2045-824X-4-20
Jerzy Krupinski, Manal Abudawood, Sabine Matou-Nasri, Raid Al-Baradie, Eugen Bogdan Petcu, Carlos Justicia, Anna Planas, Donghui Liu, Norma Rovira, Marta Grau-Slevin, Julio Secades, Mark Slevin
{"title":"Citicoline induces angiogenesis improving survival of vascular/human brain microvessel endothelial cells through pathways involving ERK1/2 and insulin receptor substrate-1.","authors":"Jerzy Krupinski, Manal Abudawood, Sabine Matou-Nasri, Raid Al-Baradie, Eugen Bogdan Petcu, Carlos Justicia, Anna Planas, Donghui Liu, Norma Rovira, Marta Grau-Slevin, Julio Secades, Mark Slevin","doi":"10.1186/2045-824X-4-20","DOIUrl":"https://doi.org/10.1186/2045-824X-4-20","url":null,"abstract":"<p><strong>Unlabelled: </strong></p><p><strong>Background: </strong>Citicoline is one of the neuroprotective agents that have been used as a therapy in stroke patients. There is limited published data describing the mechanisms through which it acts.</p><p><strong>Methods: </strong>We used in vitro angiogenesis assays: migration, proliferation, differentiation into tube-like structures in Matrigel™ and spheroid development assays in human brain microvessel endothelial cells (hCMEC/D3). Western blotting was performed on protein extraction from hCMEC/D3 stimulated with citicoline. An analysis of citicoline signalling pathways was previously studied using a Kinexus phospho-protein screening array. A staurosporin/calcium ionophore-induced apoptosis assay was performed by seeding hCMEC/D3 on to glass coverslips in serum poor medium. In a pilot in vivo study, transient MCAO in rats was carried out with and without citicoline treatment (1000 mg/Kg) applied at the time of occlusion and subsequently every 3 days until euthanasia (21 days). Vascularity of the stroke-affected regions was examined by immunohistochemistry.</p><p><strong>Results: </strong>Citicoline presented no mitogenic and chemotactic effects on hCMEC/D3; however, it significantly increased wound recovery, the formation of tube-like structures in Matrigel™ and enhanced spheroid development and sprouting. Citicoline induced the expression of phospho-extracellular-signal regulated kinase (ERK)-1/2. Kinexus assays showed an over-expression of insulin receptor substrate-1 (IRS-1). Knock-down of IRS-1 with targeted siRNA in our hCMEC/D3 inhibited the pro-angiogenic effects of citicoline. The percentage of surviving cells was higher in the presence of citicoline. Citicoline treatment significantly increased the numbers of new, active CD105-positive microvessels following MCAO.</p><p><strong>Conclusions: </strong>The findings demonstrate both a pro-angiogenic and protective effect of citicoline on hCMEC/D3 in vitro and following middle cerebral artery occlusion (MCAO) in vivo.</p>","PeriodicalId":23948,"journal":{"name":"Vascular Cell","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2012-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/2045-824X-4-20","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31113816","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Vascular CellPub Date : 2012-11-20DOI: 10.1186/2045-824X-4-19
Gerald G Behr, Leonardo Liberman, Jocelyn Compton, Maria C Garzon, Kimberly D Morel, Christine T Lauren, Thomas J Starc, Stephen J Kovacs, Vincent Beltroni, Rachel Landres, Kwame Anyane-Yeboa, Philip M Meyers, Emile Bacha, Jessica J Kandel
{"title":"CM-AVM syndrome in a neonate: case report and treatment with a novel flow reduction strategy.","authors":"Gerald G Behr, Leonardo Liberman, Jocelyn Compton, Maria C Garzon, Kimberly D Morel, Christine T Lauren, Thomas J Starc, Stephen J Kovacs, Vincent Beltroni, Rachel Landres, Kwame Anyane-Yeboa, Philip M Meyers, Emile Bacha, Jessica J Kandel","doi":"10.1186/2045-824X-4-19","DOIUrl":"https://doi.org/10.1186/2045-824X-4-19","url":null,"abstract":"<p><p> Mutations in the RASA-1 gene underlie several related disorders of vasculogenesis. Capillary malformation-arteriovenous malformation (CM-AVM) is one such entity and was recently encountered in a neonate who demonstrated its clinical and radiologic features. A single mutation in the RASA-1 gene was detected.A novel flow reduction strategy was employed to a large AVM affecting the patient's upper limb. The imaging findings, surgical procedure and patient's improved post-operative state are described.</p>","PeriodicalId":23948,"journal":{"name":"Vascular Cell","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2012-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/2045-824X-4-19","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31060523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Vascular CellPub Date : 2012-11-17DOI: 10.1186/2045-824X-4-18
Bryan Simoneau, François Houle, Jacques Huot
{"title":"Regulation of endothelial permeability and transendothelial migration of cancer cells by tropomyosin-1 phosphorylation.","authors":"Bryan Simoneau, François Houle, Jacques Huot","doi":"10.1186/2045-824X-4-18","DOIUrl":"https://doi.org/10.1186/2045-824X-4-18","url":null,"abstract":"<p><strong>Unlabelled: </strong></p><p><strong>Background: </strong>Loss of endothelial cell integrity and selective permeability barrier is an early event in the sequence of oxidant-mediated injury and may result in atherosclerosis, hypertension and facilitation of transendothelial migration of cancer cells during metastasis. We already reported that endothelial cell integrity is tightly regulated by the balanced co-activation of p38 and ERK pathways. In particular, we showed that phosphorylation of tropomyosin-1 (tropomyosin alpha-1 chain = Tm1) at Ser283 by DAP kinase, downstream of the ERK pathway might be a key event required to maintain the integrity and normal functions of the endothelium in response to oxidative stress.</p><p><strong>Methods: </strong>Endothelial permeability was assayed by monitoring the passage of Dextran-FITC through a tight monolayer of HUVECs grown to confluence in Boyden chambers. Actin and Tm1 dynamics and distribution were evaluated by immunofluorescence. We modulated the expression of Tm1 by siRNA and lentiviral-mediated expression of wild type and mutated forms of Tm1 insensitive to the siRNA. Transendothelial migration of HT-29 colon cancer cells was monitored in Boyden chambers similarly as for permeability.</p><p><strong>Results: </strong>We provide evidence indicating that Tm1 phosphorylation at Ser283 is essential to regulate endothelial permeability under oxidative stress by modulating actin dynamics. Moreover, the transendothelial migration of colon cancer cells is also regulated by the phosphorylation of Tm1 at Ser283.</p><p><strong>Conclusion: </strong>Our finding strongly support the role for the phosphorylation of endothelial Tm1 at Ser283 to prevent endothelial barrier dysfunction associated with oxidative stress injury.</p>","PeriodicalId":23948,"journal":{"name":"Vascular Cell","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2012-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/2045-824X-4-18","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31051493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Vascular CellPub Date : 2012-10-22DOI: 10.1186/2045-824X-4-17
Jan Kitajewski
{"title":"\"Large eaters\" meet blood vessels: a new thematic series on macrophages and angiogenesis.","authors":"Jan Kitajewski","doi":"10.1186/2045-824X-4-17","DOIUrl":"https://doi.org/10.1186/2045-824X-4-17","url":null,"abstract":"<p><p> Vascular Cell has launched a new series on macrophages and angiogenesis, a quickly evolving field critical to blood and lymphatic vessels during development, inflammation and tumorigenesis.</p>","PeriodicalId":23948,"journal":{"name":"Vascular Cell","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2012-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/2045-824X-4-17","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30996209","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Temporal expression analysis of angiogenesis-related genes in brain development.","authors":"Abdulkadir Ozkan, Atilla Biçer, Timuçin Avşar, Askin Seker, Zafer Orkun Toktaş, Süheyla Uyar Bozkurt, Ayse Nazli Başak, Türker Kılıç","doi":"10.1186/2045-824X-4-16","DOIUrl":"https://doi.org/10.1186/2045-824X-4-16","url":null,"abstract":"<p><strong>Unlabelled: </strong></p><p><strong>Background: </strong>The current knowledge on molecular pathogenesis of cerebral vascular malformations (CVM), which are believed to arise during development, is very limited. To unravel the molecular mechanisms involved in CVMs, a detailed understanding of the brain vascular development at molecular level is crucial. In this study, we aimed to explore the temporal and comparative expression profile of angiogenesis-related genes in the establishment of brain vasculature.</p><p><strong>Methods: </strong>Expression of a total of 113 angiogenesis-related genes during murine brain development has been analyzed using low-density array systems designed for angiogenesis-related genes. Bai1 (brain specific angiogenesis inhibitor-1), a recently identified novel anti-angiogenic gene, has been selected for further characterization.</p><p><strong>Results: </strong>We found that 62 out of 113 analyzed genes have expression in brain development at varying levels. Nineteen of these were differentially expressed between embryonic and postnatal stages (>1.5 fold). Bai1 is strongly expressed on growing blood vessels of cerebral cortex and hippocampus, partially expressed in the lateral regions of striatum, but mostly absent on the thalamus.</p><p><strong>Conclusion: </strong>By showing the comparative expression analysis of angiogenesis-related genes throughout brain development, the data presented here will be a crucial addition to further functional studies on cerebrovascular research.</p>","PeriodicalId":23948,"journal":{"name":"Vascular Cell","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2012-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/2045-824X-4-16","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30941265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Vascular CellPub Date : 2012-09-03DOI: 10.1186/2045-824X-4-14
Michael C Schmid, Judith A Varner
{"title":"Myeloid cells in tumor inflammation.","authors":"Michael C Schmid, Judith A Varner","doi":"10.1186/2045-824X-4-14","DOIUrl":"https://doi.org/10.1186/2045-824X-4-14","url":null,"abstract":"<p><p> Bone marrow derived myeloid cells progressively accumulate in tumors, where they establish an inflammatory microenvironment that is favorable for tumor growth and spread. These cells are comprised primarily of monocytic and granulocytic myeloid derived suppressor cells (MDSCs) or tumor-associated macrophages (TAMs), which are generally associated with a poor clinical outcome. MDSCs and TAMs promote tumor progression by stimulating immunosuppression, neovascularization, metastasis and resistance to anti-cancer therapy. Strategies to target the tumor-promoting functions of myeloid cells could provide substantial therapeutic benefit to cancer patients.</p>","PeriodicalId":23948,"journal":{"name":"Vascular Cell","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2012-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/2045-824X-4-14","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30873264","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Vascular CellPub Date : 2012-09-03DOI: 10.1186/2045-824X-4-15
Natasha L Harvey, Emma J Gordon
{"title":"Deciphering the roles of macrophages in developmental and inflammation stimulated lymphangiogenesis.","authors":"Natasha L Harvey, Emma J Gordon","doi":"10.1186/2045-824X-4-15","DOIUrl":"https://doi.org/10.1186/2045-824X-4-15","url":null,"abstract":"<p><p> Lymphatic vessels share an intimate relationship with hematopoietic cells that commences during embryogenesis and continues throughout life. Lymphatic vessels provide a key conduit for immune cell trafficking during immune surveillance and immune responses and in turn, signals produced by immune lineage cells in settings of inflammation regulate lymphatic vessel growth and activity. In the majority of cases, the recruitment and activation of immune cells during inflammation promotes the growth and development of lymphatic vessels (lymphangiogenesis) and enhances lymph flow, effects that amplify cell trafficking to local lymph nodes and facilitate the mounting of effective immune responses. Macrophages comprise a major, heterogeneous lineage of immune cells that, in addition to key roles in innate and adaptive immunity, perform diverse tasks important for tissue development, homeostasis and repair. Here, we highlight the emerging roles of macrophages in lymphangiogenesis, both during development and in settings of pathology. While much attention has focused on the production of pro-lymphangiogenic stimuli including VEGF-C and VEGF-D by macrophages in models of inflammation including cancer, there is ample evidence to suggest that macrophages provide additional signals important for the regulation of lymphatic vascular growth, morphogenesis and function.</p>","PeriodicalId":23948,"journal":{"name":"Vascular Cell","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2012-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/2045-824X-4-15","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30875367","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Vascular CellPub Date : 2012-08-31DOI: 10.1186/2045-824X-4-13
Andrew C Newman, Christopher C W Hughes
{"title":"Macrophages and angiogenesis: a role for Wnt signaling.","authors":"Andrew C Newman, Christopher C W Hughes","doi":"10.1186/2045-824X-4-13","DOIUrl":"https://doi.org/10.1186/2045-824X-4-13","url":null,"abstract":"<p><p> Macrophages regulate many developmental and pathological processes in both embryonic and adult tissues, and recent studies have shown a significant role in angiogenesis. Similarly, Wnt signaling is fundamental to tissue morphogenesis and also has a role in vascular development. In this review, we summarize recent advances in the field of macrophage-regulated angiogenesis, with a focus on the role of macrophage-derived Wnt ligands. We review data that provide both direct and indirect evidence for macrophage-derived Wnt regulation of physiologic and pathologic angiogenesis. Finally, we propose that Wnt signaling plays a central role in differentiation of tumor associated and wound infiltrating macrophages to a proangiogenic phenotype.</p>","PeriodicalId":23948,"journal":{"name":"Vascular Cell","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2012-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/2045-824X-4-13","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30872101","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}