Vascular Cell最新文献

{"title":"Netrin-4 promotes mural cell adhesion and recruitment to endothelial cells.","authors":"Esma Lejmi,&nbsp;Ilyes Bouras,&nbsp;Serge Camelo,&nbsp;Marie Roumieux,&nbsp;Norbert Minet,&nbsp;Carole Leré-Déan,&nbsp;Tatyana Merkulova-Rainon,&nbsp;Gwennhael Autret,&nbsp;Catherine Vayssettes,&nbsp;Olivier Clement,&nbsp;Jean Plouët,&nbsp;Laurence Leconte","doi":"10.1186/2045-824X-6-1","DOIUrl":"https://doi.org/10.1186/2045-824X-6-1","url":null,"abstract":"<p><p>Netrins are secreted molecules involved in axon guidance and angiogenesis. We previously showed that Netrin-4 acts as an anti-angiogenic factor by inhibiting endothelial cell (EC) functions. In this study, we investigated the effects of Netrin-4 on vascular smooth muscle cell (VSMC) activity in vitro and in vivo. We show that exogenous Netrin-4 stimulated VSMC adhesion and migration, and increased their coverage on EC tubes (grown on a Matrigel substrate). siRNA knock-down of endogenous Netrin-4 expression in VSMC decreased their recruitment to EC tubes. VSMC expressed Netrin-4 and three of the six Netrin-1 cognate receptors: DCC, Neogenin, and Unc5B. Silencing of these receptors reduced Netrin-4 adhesion to VSMC, strongly suggesting that these receptors were involved in the recruitment process. We previously showed that Netrin-4 overexpression in PC3 cancer cells delayed tumor growth in a model of subcutaneous xenograft by reducing tumor vessel density. Here, we show that Netrin-4 overexpression improved tumor blood vessel structure and increased VSMC coverage. Thus, Netrin-4 induced mural cell recruitment may play a role in the inhibition of tumor growth. Our data suggest that Netrin-4 is important for blood vessel normalization through the regulation of both endothelial and perivascular cells. </p>","PeriodicalId":23948,"journal":{"name":"Vascular Cell","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2014-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/2045-824X-6-1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32069356","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":"The role of tumor-associated macrophages in tumor vascularization.","authors":"Chunqing Guo, Annicole Buranych, Devanand Sarkar, Paul B Fisher, Xiang-Yang Wang","doi":"10.1186/2045-824X-5-20","DOIUrl":"10.1186/2045-824X-5-20","url":null,"abstract":"<p><p>Tumor vascularization is a highly complex process that involves the interaction between tumors and their surrounding stroma, as well as many distinct angiogenesis-regulating factors. Tumor associated macrophages (TAMs) represent one of the most abundant cell components in the tumor environment and key contributors to cancer-related inflammation. A large body of evidence supports the notion that TAMs play a critical role in promoting the formation of an abnormal tumor vascular network and subsequent tumor progression and invasion. Clinical and experimental evidence has shown that high levels of infiltrating TAMs are associated with poor patient prognosis and tumor resistance to therapies. In addition to stimulating angiogenesis during tumor growth, TAMs enhance tumor revascularization in response to cytotoxic therapy (e.g., radiotherapy), thereby causing cancer relapse. In this review, we highlight the emerging data related to the phenotype and polarization of TAMs in the tumor microenvironment, as well as the underlying mechanisms of macrophage function in the regulation of the angiogenic switch and tumor vascularization. Additionally, we discuss the potential of targeting pro-angiogenic TAMs, or reprograming TAMs toward a tumoricidal and angiostatic phenotype, to promote normalization of the tumor vasculature to enhance the outcome of cancer therapies.</p>","PeriodicalId":23948,"journal":{"name":"Vascular Cell","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2013-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3913793/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31934649","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":"The effects of radiation on angiogenesis.","authors":"Peter Grabham, Preety Sharma","doi":"10.1186/2045-824X-5-19","DOIUrl":"10.1186/2045-824X-5-19","url":null,"abstract":"<p><p>The average human body contains tens of thousands of miles of vessels that permeate every tissue down to the microscopic level. This makes the human vasculature a prime target for an agent like radiation that originates from a source and passes through the body. Exposure to radiation released during nuclear accidents and explosions, or during cancer radiotherapy, is well known to cause vascular pathologies because of the ionizing effects of electromagnetic radiations (photons) such as gamma rays. There is however, another type of less well-known radiation - charged ion particles, and these atoms stripped of electrons, have different physical properties to the photons of electromagnetic radiation. They are either found in space or created on earth by particle collider facilities, and are of significant recent interest due to their enhanced effectiveness and increasing use in cancer radiotherapy, as well as a health risk to the growing number of people spending time in the space environment. Although there is to date, relatively few studies on the effects of charged particles on the vascular system, a very different picture of the biological effects of these particles compared to photons is beginning to emerge. These under researched biological effects of ion particles have a large impact on the health consequences of exposure. In this short review, we will discuss the effects of charged particles on an important biological process of the vascular system, angiogenesis, which creates and maintains the vasculature and is highly important in tumor vasculogenesis. </p>","PeriodicalId":23948,"journal":{"name":"Vascular Cell","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2013-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3895662/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40267258","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":"Angiopoietin-1 and angiopoietin-2 are altered in polycystic ovarian syndrome (PCOS) during controlled ovarian stimulation.","authors":"Reshef Tal,&nbsp;David B Seifer,&nbsp;Richard V Grazi,&nbsp;Henry E Malter","doi":"10.1186/2045-824X-5-18","DOIUrl":"https://doi.org/10.1186/2045-824X-5-18","url":null,"abstract":"<p><p>Polycystic ovarian syndrome (PCOS) ovaries are characterized by increased angiogenesis and hypervascularity. While angiopoietin-1 (Ang-1) and its antagonist, angiopoietin-2 (Ang-2), are essential for ovarian function and angiogenesis, the levels of Ang-1 and Ang-2 in PCOS are unknown. This was a prospective cohort study of 14 PCOS women and 14 matched controls undergoing controlled ovarian stimulation (COS). Serum was collected on day 3, hCG and retrieval days. Follicular fluid (FF) was collected on retrieval day. Serum Ang-1 and Ang-2 levels were constant throughout COS, but serum Ang-1 levels were increased at all time points in PCOS women compared with controls (p < 0.05). No differences between groups were found in serum Ang-2 levels or FF Ang-1 levels. However, FF Ang-2 levels were increased almost 2-fold in PCOS women compared with controls (p < 0.01), and correlated positively with number of oocytes retrieved (r = 0.65, p < 0.0001). This study is the first to provide evidence of an alteration in the Ang-1/Ang-2 system in PCOS women. The biological role of Ang-2 in promoting capillary leakage, the increased Ang-2 FF level in PCOS, and its correlation with number of oocytes suggest that Ang-2 may play an important role in the increased risk of ovarian hyperstimulation in PCOS. </p>","PeriodicalId":23948,"journal":{"name":"Vascular Cell","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2013-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/2045-824X-5-18","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40262424","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":"Notch and VEGF pathways play distinct but complementary roles in tumor angiogenesis.","authors":"Sonia L Hernandez,&nbsp;Debarshi Banerjee,&nbsp;Alejandro Garcia,&nbsp;Thaned Kangsamaksin,&nbsp;Wei-Yi Cheng,&nbsp;Dimitris Anastassiou,&nbsp;Yasuhiro Funahashi,&nbsp;Angela Kadenhe-Chiweshe,&nbsp;Carrie J Shawber,&nbsp;Jan K Kitajewski,&nbsp;Jessica J Kandel,&nbsp;Darrell J Yamashiro","doi":"10.1186/2045-824X-5-17","DOIUrl":"https://doi.org/10.1186/2045-824X-5-17","url":null,"abstract":"<p><strong>Background: </strong>Anti-angiogenesis is a validated strategy to treat cancer, with efficacy in controlling both primary tumor growth and metastasis. The role of the Notch family of proteins in tumor angiogenesis is still emerging, but recent data suggest that Notch signaling may function in the physiologic response to loss of VEGF signaling, and thus participate in tumor adaptation to VEGF inhibitors.</p><p><strong>Methods: </strong>We asked whether combining Notch and VEGF blockade would enhance suppression of tumor angiogenesis and growth, using the NGP neuroblastoma model. NGP tumors were engineered to express a Notch1 decoy construct, which restricts Notch signaling, and then treated with either the anti-VEGF antibody bevacizumab or vehicle.</p><p><strong>Results: </strong>Combining Notch and VEGF blockade led to blood vessel regression, increasing endothelial cell apoptosis and disrupting pericyte coverage of endothelial cells. Combined Notch and VEGF blockade did not affect tumor weight, but did additively reduce tumor viability.</p><p><strong>Conclusions: </strong>Our results indicate that Notch and VEGF pathways play distinct but complementary roles in tumor angiogenesis, and show that concurrent blockade disrupts primary tumor vasculature and viability further than inhibition of either pathway alone.</p>","PeriodicalId":23948,"journal":{"name":"Vascular Cell","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2013-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/2045-824X-5-17","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31759342","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":"Two distinct types of the inhibition of vasculogenesis by different species of charged particles.","authors":"Peter Grabham, Preety Sharma, Alan Bigelow, Charles Geard","doi":"10.1186/2045-824X-5-16","DOIUrl":"10.1186/2045-824X-5-16","url":null,"abstract":"<p><strong>Background: </strong>Charged particle radiation is known to be more biologically effective than photon radiation. One example of this is the inhibition of the formation of human blood vessels. This effect is an important factor influencing human health and is relevant to space travel as well as to cancer radiotherapy. We have previously shown that ion particles with a high energy deposition, or linear energy transfer (LET) are more than four times more effective at disrupting mature vessel tissue models than particles with a lower LET. For vasculogenesis however, the relative biological effectiveness between particles is the same. This unexpected result prompted us to investigate whether the inhibition of vasculogenesis was occurring by distinct mechanisms.</p><p><strong>Methods: </strong>Using 3-Dimensional human vessel models, we developed assays that determine at what stage angiogenesis is inhibited. Vessel morphology, the presence of motile tip structures, and changes in the matrix architecture were assessed. To confirm that the mechanisms are distinct, stimulation of Protein Kinase C (PKC) with phorbol ester (PMA) was employed to selectively restore vessel formation in cultures where early motile tip activity was inhibited.</p><p><strong>Results: </strong>Endothelial cells in 3-D culture exposed to low LET protons failed to make connections with other cells but eventually developed a central lumen. Conversely, cells exposed to high LET Fe charged particles extended cellular processes and made connections to other cells but did not develop a central lumen. The microtubule and actin cytoskeletons indicated that motility at the extending tips of endothelial cells is inhibited by low LET but not high LET particles. Actin-rich protrusive structures that contain bundled microtubules showed a 65% decrease when exposed to low LET particles but not high LET particles, with commensurate changes in the matrix architecture. Stimulation of PKC with PMA restored tip motility and capillary formation in low but not high LET particle treated cultures.</p><p><strong>Conclusion: </strong>Low LET charged particles inhibit the early stages of vasculogenesis when tip cells have motile protrusive structures and are creating pioneer guidance tunnels through the matrix. High LET charged particles do not affect the early stages of vasculogenesis but they do affect the later stages when the endothelial cells migrate to form tubes.</p>","PeriodicalId":23948,"journal":{"name":"Vascular Cell","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2013-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/2045-824X-5-16","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31740401","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":"Cardiac angiogenesis directed by stable Hypoxia Inducible Factor-1.","authors":"Chad B Walton,&nbsp;Jennifer Ecker,&nbsp;Cynthia D Anderson,&nbsp;Joel T Outten,&nbsp;Randall Z Allison,&nbsp;Ralph V Shohet","doi":"10.1186/2045-824X-5-15","DOIUrl":"https://doi.org/10.1186/2045-824X-5-15","url":null,"abstract":"<p><strong>Background: </strong>The heterodimeric, oxygen-sensitive transcription factor Hypoxia Inducible Factor-1 (HIF-1) orchestrates angiogenesis and plays a key role in the response to ischemia and the growth of cancers.</p><p><strong>Methods: </strong>We developed a transgenic mouse line in which expression of an oxygen-stable HIF-1α construct was controlled by a tetracycline-responsive promoter. HIF-1α expression was induced for up to 28 days in adult mouse heart, resulting in angiogenesis and progressive ventricular dysfunction.</p><p><strong>Results: </strong>Gross inspection demonstrated enlarged hearts with large epicardial vessels with prominent side branches. Perfusion curves obtained by ultrasound contrast analysis demonstrated a significant increase in the myocardial red cell volume after 28 days of HIF-1α expression. Corrosion casts of cardiac vessels were made with a new low-viscosity resin that can fill the vasculature down to the level of the capillaries. Scanning electron microscopy of these casts reveal \"lakes\" of capillaries forming off of larger vessels after HIF expression, and support the rapid formation of mature neovascularization. Pro-angiogenic factors DLL-4, Notch-1, and PDGF-β, were evaluated by immunohistochemistry and Western blots, and support a pattern of progressive functional neoangiogenesis.</p><p><strong>Conclusions: </strong>This study demonstrates the structural characteristics of HIF-directed angiogenesis and supports the utility of manipulation of HIF signaling to enhance perfusion and treat ischemia.</p>","PeriodicalId":23948,"journal":{"name":"Vascular Cell","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2013-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/2045-824X-5-15","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31691903","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":"Lymphatics in health and disease: a new thematic series in vascular cell.","authors":"Jan Kitajewski,&nbsp;Carrie J Shawber,&nbsp;Michael Simons","doi":"10.1186/2045-824X-5-14","DOIUrl":"https://doi.org/10.1186/2045-824X-5-14","url":null,"abstract":"<p><p>Vascular Cell is launching new series on lymphatics, a vascular system required for physiological fluid balance and immunity, and whose damage leads to edema. </p>","PeriodicalId":23948,"journal":{"name":"Vascular Cell","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2013-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/2045-824X-5-14","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31606577","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":"Arteriogenic therapy based on simultaneous delivery of VEGF-A and FGF4 genes improves the recovery from acute limb ischemia.","authors":"Agnieszka Jazwa,&nbsp;Mateusz Tomczyk,&nbsp;Hevidar M Taha,&nbsp;Elisa Hytonen,&nbsp;Mateusz Stoszko,&nbsp;Lorena Zentilin,&nbsp;Mauro Giacca,&nbsp;Seppo Yla-Herttuala,&nbsp;Costanza Emanueli,&nbsp;Alicja Jozkowicz,&nbsp;Jozef Dulak","doi":"10.1186/2045-824X-5-13","DOIUrl":"https://doi.org/10.1186/2045-824X-5-13","url":null,"abstract":"<p><strong>Background: </strong>Gene therapy stimulating the growth of blood vessels is considered for the treatment of peripheral and myocardial ischemia. Here we aimed to achieve angiogenic synergism between vascular endothelial growth factor-A (VEGF-A, VEGF) and fibroblast growth factor 4 (FGF4) in murine normoperfused and ischemic limb muscles.</p><p><strong>Methods: </strong>Adeno-associated viral vectors (AAVs) carrying β-galactosidase gene (AAV-LacZ), VEGF-A (AAV-VEGF-A) or two angiogenic genes (AAV-FGF4-IRES-VEGF-A) were injected into the normo-perfused adductor muscles of C57Bl/6 mice. Moreover, in a different experiment, mice were subjected to unilateral hindlimb ischemia by femoral artery ligation followed by intramuscular injections of AAV-LacZ, AAV-VEGF-A or AAV-FGF4-IRES-VEGF-A below the site of ligation. Post-ischemic blood flow recovery was assessed sequentially by color laser Doppler. Mice were monitored for 28 days.</p><p><strong>Results: </strong>VEGF-A delivered alone (AAV-VEGF-A) or in combination with FGF4 (AAV-FGF4-IRES-VEGF-A) increased the number of capillaries in normo-perfused hindlimbs when compared to AAV-LacZ. Simultaneous overexpression of both agents (VEGF-A and FGF4) stimulated the capillary wall remodeling in the non-ischemic model. Moreover, AAV-FGF4-IRES-VEGF-A faster restored the post-ischemic foot blood flow and decreased the incidence of toe necrosis in comparison to AAV-LacZ.</p><p><strong>Conclusions: </strong>Synergy between VEGF-A and FGF4 to produce stable and functional blood vessels may be considered a promising option in cardiovascular gene therapy.</p>","PeriodicalId":23948,"journal":{"name":"Vascular Cell","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2013-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/2045-824X-5-13","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31547825","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":"Correction: The importance of microglia in the development of the vasculature in the central nervous system.","authors":"Tom Arnold,&nbsp;Christer Betsholtz","doi":"10.1186/2045-824X-5-12","DOIUrl":"https://doi.org/10.1186/2045-824X-5-12","url":null,"abstract":"<p><strong>Correction: </strong>After the publication of this work 1 it was brought to our attention that citations in the article were not correspondingly numbered in the reference list. To avoid confusion, the article is republished here in its entirety, with the citations referenced correctly.The Publisher and authors apologize to the readers for the inconvenience caused.</p><p><strong>Abstract: </strong>The body's vascular system is thought to have developed in order to supply oxygen and nutrients to cells beyond the reach of simple diffusion. Hence, relative hypoxia in the growing central nervous system (CNS) is a major driving force for the ingression and refinement of the complex vascular bed that serves it. However, even before the establishment of this CNS vascular system, CNS-specific macrophages (microglia) migrate into the brain. Recent studies in mice point to the fundamental importance of microglia in shaping CNS vasculature during development, and re-shaping these vessels during pathological insults. In this review, we discuss the origin of CNS microglia and their localization within the brain based on data obtained in mice. We then review evidence supporting a functional role of these microglia in developmental angiogenesis. Although pathologic processes such as CNS ischemia may subvert the developmental functions of microglia/macrophages with significant effects on brain neo-angiogenesis, we have left this topic to other recent reviews 23.</p>","PeriodicalId":23948,"journal":{"name":"Vascular Cell","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2013-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/2045-824X-5-12","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31542002","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}