The Experts below are selected from a list of 591 Experts worldwide ranked by ideXlab platform
Valentin Djonov - One of the best experts on this subject based on the ideXlab platform.
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SDF-1/CXCR4 signalling is involved in blood vessel growth and remodelling by intussusception.
Journal of cellular and molecular medicine, 2019Co-Authors: Ivanka Dimova, Andrew N. Makanya, Ruslan Hlushchuk, Swapna Karthik, David Semela, Vladislav Volarevic, Valentin DjonovAbstract:The precise mechanisms of SDF-1 (CXCL12) in Angiogenesis are not fully elucidated. Recently, we showed that Notch inhibition induces extensive Intussusceptive Angiogenesis by recruitment of mononuclear cells and it was associated with increased levels of SDF-1 and CXCR4. In the current study, we demonstrated SDF-1 expression in liver sinusoidal vessels of Notch1 knockout mice with regenerative hyperplasia by means of intussusception, but we did not detect any SDF-1 expression in wild-type mice with normal liver vessel structure. In addition, pharmacological inhibition of SDF-1/CXCR4 signalling by AMD3100 perturbs Intussusceptive vascular growth and abolishes mononuclear cell recruitment in the chicken area vasculosa. In contrast, treatment with recombinant SDF-1 protein increased microvascular density by 34% through augmentation of pillar number compared to controls. The number of extravasating mononuclear cells was four times higher after SDF-1 application and two times less after blocking this pathway. Bone marrow-derived mononuclear cells (BMDC) were recruited to vessels in response to elevated expression of SDF-1 in endothelial cells. They participated in formation and stabilization of pillars. The current study is the first report to implicate SDF-1/CXCR4 signalling in Intussusceptive Angiogenesis and further highlights the stabilizing role of BMDC in the formation of pillars during vascular remodelling.
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Publisher Correction: Synergistic interaction of sprouting and Intussusceptive Angiogenesis during zebrafish caudal vein plexus development.
Scientific reports, 2019Co-Authors: Swapna Karthik, Nenad Filipovic, Andrew N. Makanya, Ruslan Hlushchuk, Tijana Djukic, Jun-dae Kim, Adolfo Odriozola, Suk Won Jin, Benoît. Zuber, Valentin DjonovAbstract:A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
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Synergistic interaction of sprouting and Intussusceptive Angiogenesis during zebrafish caudal vein plexus development
Nature Publishing Group, 2018Co-Authors: Swapna Karthik, Nenad Filipovic, Ruslan Hlushchuk, Tijana Djukic, Jun-dae Kim, Benoît Zuber, Andrew Makanya, Adolfo Odriozola, Suk Won Jin, Valentin DjonovAbstract:Abstract Intussusceptive Angiogenesis (IA) is a complementary method to sprouting Angiogenesis (SA). The hallmark of IA is formation of trans-capillary tissue pillars, their fusion and remodeling of the vascular plexus. In this study, we investigate the formation of the zebrafish caudal vein plexus (CVP) in Tg(fli1a:eGFP) y7 and the synergistic interaction of IA and SA in crafting the archetypical angio-architecture of the CVP. Dynamic in vivo observations and quantitative analyses revealed that the primitive CVP during development was initiated through SA. Further vascular growth and remodeling occurred by IA. Intussusception contributed to the expansion of the CVP by formation of new pillars. Those pillars arose in front of the already existing ones; and in a subsequent step the serried pillars elongated and fused together. This resulted in segregation of larger vascular segments and remodelling of the disorganized vascular meshwork into hierarchical tree-like arrangement. Blood flow was the main driving force for IA, particularly shear stress geometry at the site of pillar formation and fusion. Computational simulations based on hemodynamics showed drop in shear stress levels at locations of new pillar formation, pillar elongation and fusion. Correlative 3D serial block face scanning electron microscopy confirmed the morphological substrate of the phenomena of the pillar formation observed in vivo. The data obtained demonstrates that after the sprouting phase and formation of the primitive capillary meshwork, the hemodynamic conditions enhance Intussusceptive segregation of hierarchical vascular tree i.e. Intussusceptive arborization resulting in complex vascular structures with specific angio-architecture
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Endoglin inhibition leads to Intussusceptive Angiogenesis via activation of factors related to COUP-TFII signaling pathway.
PloS one, 2017Co-Authors: Ruslan Hlushchuk, Andrew N. Makanya, Monika Wnuk, Uyen Huynh-do, Beata Styp-rekowska, Jehona Dzambazi, Valentin DjonovAbstract:Angiogenesis is a highly coordinated, extremely complex process orchestrated by multiple signaling molecules and blood flow conditions. While sprouting mode of Angiogenesis is very well investigated, the molecular mechanisms underlying intussusception, the second mode of Angiogenesis, remain largely unclear. In the current study two molecules involved in vascular growth and differentiation, namely endoglin (ENG/CD105) and chicken ovalbumin upstream promoter transcription factor II (COUP-TFII) were examined to unravel their specific roles in Angiogenesis. Down- respectively up-regulation of both molecules tightly correlates with Intussusceptive microvascular growth. Upon ENG inhibition in chicken embryo model, formation of irregular capillary meshwork accompanied by increased expression of COUP-TFII could be observed. This dynamic expression pattern of ENG and COUP-TFII during vascular development and remodeling correlated with formation of pillars and progression of Intussusceptive Angiogenesis. Similar findings could be observed in mammalian model of acute rat Thy1.1 glomerulonephritis, which was induced by intravenous injection of anti-Thy1 antibody and has shown upregulation of COUP-TFII in initial phase of intussusception, while ENG expression was not disturbed compared to the controls but decreased over the time of pillar formation. In this study, we have shown that ENG inhibition and at the same time up-regulation of COUP-TFII expression promotes Intussusceptive Angiogenesis.
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Endoglin inhibition leads to Intussusceptive Angiogenesis via activation of factors related to COUP-TFII signaling pathway - Fig 7
2017Co-Authors: Ruslan Hlushchuk, Monika Wnuk, Uyen Huynh-do, Beata Styp-rekowska, Jehona Dzambazi, Andrew Makanya, Valentin DjonovAbstract:7.1 a-d and f: rat glomeruli casts. a: control animal, b, c, e, f: different stages of Thy1.1nephropathy, e: detail from picture D (day 14 after treatment with anti-Thy1.1 antibody). Indicated are: small holes with arrows (pillars), small capillary loops with arrowheads, asterisk for glomerular microaneurysm at D5. 7.2: Fold change in gene expression of ENG, COUP-TFII, VEGFR2 and Notch in the kidney cortex of rats with Thy1.1 nephropathy compared to healthy control group (n = 4). Below the time course in days is indicated.
Ruslan Hlushchuk - One of the best experts on this subject based on the ideXlab platform.
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SDF-1/CXCR4 signalling is involved in blood vessel growth and remodelling by intussusception.
Journal of cellular and molecular medicine, 2019Co-Authors: Ivanka Dimova, Andrew N. Makanya, Ruslan Hlushchuk, Swapna Karthik, David Semela, Vladislav Volarevic, Valentin DjonovAbstract:The precise mechanisms of SDF-1 (CXCL12) in Angiogenesis are not fully elucidated. Recently, we showed that Notch inhibition induces extensive Intussusceptive Angiogenesis by recruitment of mononuclear cells and it was associated with increased levels of SDF-1 and CXCR4. In the current study, we demonstrated SDF-1 expression in liver sinusoidal vessels of Notch1 knockout mice with regenerative hyperplasia by means of intussusception, but we did not detect any SDF-1 expression in wild-type mice with normal liver vessel structure. In addition, pharmacological inhibition of SDF-1/CXCR4 signalling by AMD3100 perturbs Intussusceptive vascular growth and abolishes mononuclear cell recruitment in the chicken area vasculosa. In contrast, treatment with recombinant SDF-1 protein increased microvascular density by 34% through augmentation of pillar number compared to controls. The number of extravasating mononuclear cells was four times higher after SDF-1 application and two times less after blocking this pathway. Bone marrow-derived mononuclear cells (BMDC) were recruited to vessels in response to elevated expression of SDF-1 in endothelial cells. They participated in formation and stabilization of pillars. The current study is the first report to implicate SDF-1/CXCR4 signalling in Intussusceptive Angiogenesis and further highlights the stabilizing role of BMDC in the formation of pillars during vascular remodelling.
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Publisher Correction: Synergistic interaction of sprouting and Intussusceptive Angiogenesis during zebrafish caudal vein plexus development.
Scientific reports, 2019Co-Authors: Swapna Karthik, Nenad Filipovic, Andrew N. Makanya, Ruslan Hlushchuk, Tijana Djukic, Jun-dae Kim, Adolfo Odriozola, Suk Won Jin, Benoît. Zuber, Valentin DjonovAbstract:A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
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Synergistic interaction of sprouting and Intussusceptive Angiogenesis during zebrafish caudal vein plexus development
Nature Publishing Group, 2018Co-Authors: Swapna Karthik, Nenad Filipovic, Ruslan Hlushchuk, Tijana Djukic, Jun-dae Kim, Benoît Zuber, Andrew Makanya, Adolfo Odriozola, Suk Won Jin, Valentin DjonovAbstract:Abstract Intussusceptive Angiogenesis (IA) is a complementary method to sprouting Angiogenesis (SA). The hallmark of IA is formation of trans-capillary tissue pillars, their fusion and remodeling of the vascular plexus. In this study, we investigate the formation of the zebrafish caudal vein plexus (CVP) in Tg(fli1a:eGFP) y7 and the synergistic interaction of IA and SA in crafting the archetypical angio-architecture of the CVP. Dynamic in vivo observations and quantitative analyses revealed that the primitive CVP during development was initiated through SA. Further vascular growth and remodeling occurred by IA. Intussusception contributed to the expansion of the CVP by formation of new pillars. Those pillars arose in front of the already existing ones; and in a subsequent step the serried pillars elongated and fused together. This resulted in segregation of larger vascular segments and remodelling of the disorganized vascular meshwork into hierarchical tree-like arrangement. Blood flow was the main driving force for IA, particularly shear stress geometry at the site of pillar formation and fusion. Computational simulations based on hemodynamics showed drop in shear stress levels at locations of new pillar formation, pillar elongation and fusion. Correlative 3D serial block face scanning electron microscopy confirmed the morphological substrate of the phenomena of the pillar formation observed in vivo. The data obtained demonstrates that after the sprouting phase and formation of the primitive capillary meshwork, the hemodynamic conditions enhance Intussusceptive segregation of hierarchical vascular tree i.e. Intussusceptive arborization resulting in complex vascular structures with specific angio-architecture
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Endoglin inhibition leads to Intussusceptive Angiogenesis via activation of factors related to COUP-TFII signaling pathway.
PloS one, 2017Co-Authors: Ruslan Hlushchuk, Andrew N. Makanya, Monika Wnuk, Uyen Huynh-do, Beata Styp-rekowska, Jehona Dzambazi, Valentin DjonovAbstract:Angiogenesis is a highly coordinated, extremely complex process orchestrated by multiple signaling molecules and blood flow conditions. While sprouting mode of Angiogenesis is very well investigated, the molecular mechanisms underlying intussusception, the second mode of Angiogenesis, remain largely unclear. In the current study two molecules involved in vascular growth and differentiation, namely endoglin (ENG/CD105) and chicken ovalbumin upstream promoter transcription factor II (COUP-TFII) were examined to unravel their specific roles in Angiogenesis. Down- respectively up-regulation of both molecules tightly correlates with Intussusceptive microvascular growth. Upon ENG inhibition in chicken embryo model, formation of irregular capillary meshwork accompanied by increased expression of COUP-TFII could be observed. This dynamic expression pattern of ENG and COUP-TFII during vascular development and remodeling correlated with formation of pillars and progression of Intussusceptive Angiogenesis. Similar findings could be observed in mammalian model of acute rat Thy1.1 glomerulonephritis, which was induced by intravenous injection of anti-Thy1 antibody and has shown upregulation of COUP-TFII in initial phase of intussusception, while ENG expression was not disturbed compared to the controls but decreased over the time of pillar formation. In this study, we have shown that ENG inhibition and at the same time up-regulation of COUP-TFII expression promotes Intussusceptive Angiogenesis.
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Endoglin inhibition leads to Intussusceptive Angiogenesis via activation of factors related to COUP-TFII signaling pathway - Fig 7
2017Co-Authors: Ruslan Hlushchuk, Monika Wnuk, Uyen Huynh-do, Beata Styp-rekowska, Jehona Dzambazi, Andrew Makanya, Valentin DjonovAbstract:7.1 a-d and f: rat glomeruli casts. a: control animal, b, c, e, f: different stages of Thy1.1nephropathy, e: detail from picture D (day 14 after treatment with anti-Thy1.1 antibody). Indicated are: small holes with arrows (pillars), small capillary loops with arrowheads, asterisk for glomerular microaneurysm at D5. 7.2: Fold change in gene expression of ENG, COUP-TFII, VEGFR2 and Notch in the kidney cortex of rats with Thy1.1 nephropathy compared to healthy control group (n = 4). Below the time course in days is indicated.
Andrew N. Makanya - One of the best experts on this subject based on the ideXlab platform.
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SDF-1/CXCR4 signalling is involved in blood vessel growth and remodelling by intussusception.
Journal of cellular and molecular medicine, 2019Co-Authors: Ivanka Dimova, Andrew N. Makanya, Ruslan Hlushchuk, Swapna Karthik, David Semela, Vladislav Volarevic, Valentin DjonovAbstract:The precise mechanisms of SDF-1 (CXCL12) in Angiogenesis are not fully elucidated. Recently, we showed that Notch inhibition induces extensive Intussusceptive Angiogenesis by recruitment of mononuclear cells and it was associated with increased levels of SDF-1 and CXCR4. In the current study, we demonstrated SDF-1 expression in liver sinusoidal vessels of Notch1 knockout mice with regenerative hyperplasia by means of intussusception, but we did not detect any SDF-1 expression in wild-type mice with normal liver vessel structure. In addition, pharmacological inhibition of SDF-1/CXCR4 signalling by AMD3100 perturbs Intussusceptive vascular growth and abolishes mononuclear cell recruitment in the chicken area vasculosa. In contrast, treatment with recombinant SDF-1 protein increased microvascular density by 34% through augmentation of pillar number compared to controls. The number of extravasating mononuclear cells was four times higher after SDF-1 application and two times less after blocking this pathway. Bone marrow-derived mononuclear cells (BMDC) were recruited to vessels in response to elevated expression of SDF-1 in endothelial cells. They participated in formation and stabilization of pillars. The current study is the first report to implicate SDF-1/CXCR4 signalling in Intussusceptive Angiogenesis and further highlights the stabilizing role of BMDC in the formation of pillars during vascular remodelling.
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Publisher Correction: Synergistic interaction of sprouting and Intussusceptive Angiogenesis during zebrafish caudal vein plexus development.
Scientific reports, 2019Co-Authors: Swapna Karthik, Nenad Filipovic, Andrew N. Makanya, Ruslan Hlushchuk, Tijana Djukic, Jun-dae Kim, Adolfo Odriozola, Suk Won Jin, Benoît. Zuber, Valentin DjonovAbstract:A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
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Endoglin inhibition leads to Intussusceptive Angiogenesis via activation of factors related to COUP-TFII signaling pathway.
PloS one, 2017Co-Authors: Ruslan Hlushchuk, Andrew N. Makanya, Monika Wnuk, Uyen Huynh-do, Beata Styp-rekowska, Jehona Dzambazi, Valentin DjonovAbstract:Angiogenesis is a highly coordinated, extremely complex process orchestrated by multiple signaling molecules and blood flow conditions. While sprouting mode of Angiogenesis is very well investigated, the molecular mechanisms underlying intussusception, the second mode of Angiogenesis, remain largely unclear. In the current study two molecules involved in vascular growth and differentiation, namely endoglin (ENG/CD105) and chicken ovalbumin upstream promoter transcription factor II (COUP-TFII) were examined to unravel their specific roles in Angiogenesis. Down- respectively up-regulation of both molecules tightly correlates with Intussusceptive microvascular growth. Upon ENG inhibition in chicken embryo model, formation of irregular capillary meshwork accompanied by increased expression of COUP-TFII could be observed. This dynamic expression pattern of ENG and COUP-TFII during vascular development and remodeling correlated with formation of pillars and progression of Intussusceptive Angiogenesis. Similar findings could be observed in mammalian model of acute rat Thy1.1 glomerulonephritis, which was induced by intravenous injection of anti-Thy1 antibody and has shown upregulation of COUP-TFII in initial phase of intussusception, while ENG expression was not disturbed compared to the controls but decreased over the time of pillar formation. In this study, we have shown that ENG inhibition and at the same time up-regulation of COUP-TFII expression promotes Intussusceptive Angiogenesis.
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Escape mechanisms after antiangiogenic treatment, or why are the tumors growing again?
The International Journal of Developmental Biology, 2011Co-Authors: Ruslan Hlushchuk, Andrew N. Makanya, Valentin DjonovAbstract:Inhibitors of Angiogenesis and radiation induce compensatory changes in the tumor vasculature both during and after cessation of treatment. In numerous preclinical studies, Angiogenesis inhibitors were shown to be efficient in the treatment of many pathological conditions, including solid cancers. In most clinical trials, however, this approach turned out to have no significant effect, especially if applied as monotherapy. Recovery of tumors after therapy is a major problem in the management of cancer patients. The mechanisms underlying tumor recovery (or therapy resistance) have not yet been explicitly elucidated. This review deals with the transient switch from sprouting to Intussusceptive Angiogenesis, which may be an adaptive response of tumor vasculature to cancer therapy that allows the vasculature to maintain its functional properties. Potential candidates for molecular targeting of this angioadaptive mechanism are yet to be elucidated in order to improve the currently poor efficacy of contemporary antiangiogenic therapies.
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Intussusceptive Angiogenesis and its role in vascular morphogenesis, patterning, and remodeling
Angiogenesis, 2009Co-Authors: Andrew N. Makanya, Ruslan Hlushchuk, Valentin G. DjonovAbstract:New blood vessels arise initially as blood islands in the process known as vasculogenesis or as new capillary segments produced through Angiogenesis. Angiogenesis itself encompasses two broad processes, namely sprouting (SA) and Intussusceptive (IA) Angiogenesis. Primordial capillary plexuses expand through both SA and IA, but subsequent growth and remodeling are achieved through IA. The latter process proceeds through transluminal tissue pillar formation and subsequent vascular splitting, and the direction taken by the pillars delineates IA into overt phases, namely: Intussusceptive microvascular growth, Intussusceptive arborization, and Intussusceptive branching remodeling. Intussusceptive microvascular growth circumscribes the process of initiation of pillar formation and their subsequent expansion with the result that the capillary surface area is greatly enhanced. In contrast, Intussusceptive arborization entails formation of serried pillars that remodel the disorganized vascular meshwork into the typical tree-like arrangement. Optimization of local vascular branching geometry occurs through Intussusceptive branching remodeling so that the vasculature is remodeled to meet the local demand. In addition, IA is important in creation of the local organ-specific angioarchitecture. While hemodynamic forces have proven direct effects on IA, with increase in blood flow resulting in initiation of pillars, the preponderant mechanisms are unclear. Molecular control of IA has so far not been unequivocally elucidated but interplay among several factors is probably involved. Future investigations are strongly encouraged to focus on interactions among angiogenic growth factors, angiopoetins, and related receptors.
Moritz A. Konerding - One of the best experts on this subject based on the ideXlab platform.
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Intussusceptive Angiogenesis: expansion and remodeling of microvascular networks
Angiogenesis, 2014Co-Authors: Steven J. Mentzer, Moritz A. KonerdingAbstract:Intussusceptive Angiogenesis is a dynamic intravascular process capable of dramatically modifying the structure of the microcirculation. The distinctive structural feature of Intussusceptive Angiogenesis is the Intussusceptive pillar—a cylindrical microstructure that spans the lumen of small vessels and capillaries. The extension of the Intussusceptive pillar appears to be a mechanism for pruning redundant or inefficient vessels, modifying the branch angle of bifurcating vessels and duplicating existing vessels. Despite the biological importance and therapeutic potential, Intussusceptive Angiogenesis remains a mystery, in part, because it is an intravascular process that is unseen by conventional light microscopy. Here, we review several fundamental questions in the context of our current understanding of both Intussusceptive and sprouting Angiogenesis. (1) What are the physiologic signals that trigger pillar formation? (2) What endothelial and blood flow conditions specify pillar location? (3) How do pillars respond to the mechanical influence of blood flow? (4) What biological influences contribute to pillar extension? The answers to these questions are likely to provide important insights into the structure and function of microvascular networks.
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Stretch-induced intussuceptive and sprouting Angiogenesis in the chick chorioallantoic membrane.
Microvascular research, 2014Co-Authors: Janeil Belle, Nenad Filipovic, Akira Tsuda, Maximilian Ackermann, Alexandra B. Ysasi, Robert D. Bennett, Mohammad Imani Nejad, David L. Trumper, Willi L. Wagner, Moritz A. KonerdingAbstract:Abstract Vascular systems grow and remodel in response to not only metabolic needs, but also mechanical influences as well. Here, we investigated the influence of tissue-level mechanical forces on the patterning and structure of the chick chorioallantoic membrane (CAM) microcirculation. A dipole stretch field was applied to the CAM using custom computer-controlled servomotors. The topography of the stretch field was mapped using finite element models. After 3 days of stretch, Sholl analysis of the CAM demonstrated a 7-fold increase in conducting vessel intersections within the stretch field (p 0.05). In contrast, corrosion casting and SEM of the stretch field capillary meshwork demonstrated intense sprouting and Intussusceptive Angiogenesis. Both planar surface area (p
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Imaging Angiogenesis: perspectives and opportunities in tumour research - a method display.
Journal of cranio-maxillo-facial surgery : official publication of the European Association for Cranio-Maxillo-Facial Surgery, 2014Co-Authors: Andreas Pabst, Maximilian Ackermann, Willi L. Wagner, David Haberthür, Thomas Ziebart, Moritz A. KonerdingAbstract:The growth of solid tumours necessitates Angiogenesis. The aim of this paper is the presentation and evaluation of different ex vivo methods for analysing tumour Angiogenesis. Oral squamous cell carcinomas (SCC) were induced in mice by subcutaneous injection of tumour cells in the groin region and processed for histology and microvascular corrosion casting. Vascularization was analysed light microscopically using CD31 immunochemistry. Corrosion casts were analysed by scanning electron microscopy (SEM), micro computed tomography (μCT) and synchrotron radiation-based micro computed tomography (SRμCT). Immunochemistry allows for a simple and authentic detection and stereological quantification of the SCC vascularization. μCT imaging of the corrosion casts gives a high-quality overview over the three-dimensional (3D) microvascular architecture. SEM and SRμCT allow a high-definition display of the vessel morphology, providing magnificent detail recognition down to the capillary level enabling imaging of different forms of tumour Angiogenesis, e.g., sprouting and Intussusceptive Angiogenesis. Immunochemistry and SEM are regarded as suitable for most of the morphometrical and morphological assessments because of the simple procedure and the high explanatory power, especially in combination with each other. High resolution SRμCT helps answering specialized questions, however, requires sophisticated data processing for visualization and is of limited availability.
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Intussusceptive remodeling of vascular branch angles in chemically-induced murine colitis.
Microvascular research, 2013Co-Authors: Maximilian Ackermann, Akira Tsuda, Steven J. Mentzer, Timothy W. Secomb, Moritz A. KonerdingAbstract:Intussusceptive Angiogenesis is a developmental process linked to both blood vessel replication and remodeling in development. To investigate the prediction that the process of Intussusceptive Angiogenesis is associated with vessel angle remodeling in adult mice, we systematically evaluated corrosion casts of the mucosal plexus in mice with trinitrobenzesulfonic acid (TNBS)-induced and dextran sodium sulfate (DSS)-induced colitis. The mice demonstrated a significant decrease in vessel angles in both TNBS-induced and DSS-induced colitis within 4 weeks of the onset of colitis (p
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Anti-VEGFR2 and anti-IGF-1R-Adnectins inhibit Ewing’s sarcoma A673-xenograft growth and normalize tumor vascular architecture
Angiogenesis, 2012Co-Authors: Maximilian Ackermann, Brent A. Morse, Vera Delventhal, Irvith M. Carvajal, Moritz A. KonerdingAbstract:Increasing experimental evidence suggests that IGF-1 may modulate tumor Angiogenesis via activation of the expression of VEGF in Ewing sarcomas and rhabdomyosarcomas. This study investigates the effects of the PEGylated Adnectins™ CT-322, a VEGFR2-inhibitor and AT580Peg40, an IGF-1R inhibitor, as monotherapy and in combination in a murine A673 xenograft tumor model. The combination of Adnectins CT-322 and AT580Peg40 revealed a 83 % reduction in tumor growth, a nearly 5 times lower vessel density, less necrotic areas and less appearance of Intussusceptive Angiogenesis. Monotherapy with IGF-1R or CT-322 revealed equally a significant inhibition of tumor and vessel growth. Combinatory inhibition of IGF-1R and VEGFR2 shows a downregulation of IGF-binding protein 2 and a compensatory upregulation of VEGF levels. Immunohistological analysis showed remodeling vascular effects of CT-322-treatment or combination therapy. The vascular architecture in Adnectin-treated tumors was characterized by a strong normalization of vasculature. 3D-evaluation in microvascular corrosion casts showed significantly higher intervascular and interbranching distances in Adnectin-treated tumors. CT-322-treatment and combinatory inhibition reveal a significant reduction of Intussusceptive Angiogenesis. These pronounced effects on tumor vasculature suggest potential therapeutic benefit of combinatorial IGF1- and VEGF- pathways inhibition in Ewing’s sarcoma.
Nenad Filipovic - One of the best experts on this subject based on the ideXlab platform.
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Publisher Correction: Synergistic interaction of sprouting and Intussusceptive Angiogenesis during zebrafish caudal vein plexus development.
Scientific reports, 2019Co-Authors: Swapna Karthik, Nenad Filipovic, Andrew N. Makanya, Ruslan Hlushchuk, Tijana Djukic, Jun-dae Kim, Adolfo Odriozola, Suk Won Jin, Benoît. Zuber, Valentin DjonovAbstract:A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
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Synergistic interaction of sprouting and Intussusceptive Angiogenesis during zebrafish caudal vein plexus development
Nature Publishing Group, 2018Co-Authors: Swapna Karthik, Nenad Filipovic, Ruslan Hlushchuk, Tijana Djukic, Jun-dae Kim, Benoît Zuber, Andrew Makanya, Adolfo Odriozola, Suk Won Jin, Valentin DjonovAbstract:Abstract Intussusceptive Angiogenesis (IA) is a complementary method to sprouting Angiogenesis (SA). The hallmark of IA is formation of trans-capillary tissue pillars, their fusion and remodeling of the vascular plexus. In this study, we investigate the formation of the zebrafish caudal vein plexus (CVP) in Tg(fli1a:eGFP) y7 and the synergistic interaction of IA and SA in crafting the archetypical angio-architecture of the CVP. Dynamic in vivo observations and quantitative analyses revealed that the primitive CVP during development was initiated through SA. Further vascular growth and remodeling occurred by IA. Intussusception contributed to the expansion of the CVP by formation of new pillars. Those pillars arose in front of the already existing ones; and in a subsequent step the serried pillars elongated and fused together. This resulted in segregation of larger vascular segments and remodelling of the disorganized vascular meshwork into hierarchical tree-like arrangement. Blood flow was the main driving force for IA, particularly shear stress geometry at the site of pillar formation and fusion. Computational simulations based on hemodynamics showed drop in shear stress levels at locations of new pillar formation, pillar elongation and fusion. Correlative 3D serial block face scanning electron microscopy confirmed the morphological substrate of the phenomena of the pillar formation observed in vivo. The data obtained demonstrates that after the sprouting phase and formation of the primitive capillary meshwork, the hemodynamic conditions enhance Intussusceptive segregation of hierarchical vascular tree i.e. Intussusceptive arborization resulting in complex vascular structures with specific angio-architecture
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Stretch-induced intussuceptive and sprouting Angiogenesis in the chick chorioallantoic membrane.
Microvascular research, 2014Co-Authors: Janeil Belle, Nenad Filipovic, Akira Tsuda, Maximilian Ackermann, Alexandra B. Ysasi, Robert D. Bennett, Mohammad Imani Nejad, David L. Trumper, Willi L. Wagner, Moritz A. KonerdingAbstract:Abstract Vascular systems grow and remodel in response to not only metabolic needs, but also mechanical influences as well. Here, we investigated the influence of tissue-level mechanical forces on the patterning and structure of the chick chorioallantoic membrane (CAM) microcirculation. A dipole stretch field was applied to the CAM using custom computer-controlled servomotors. The topography of the stretch field was mapped using finite element models. After 3 days of stretch, Sholl analysis of the CAM demonstrated a 7-fold increase in conducting vessel intersections within the stretch field (p 0.05). In contrast, corrosion casting and SEM of the stretch field capillary meshwork demonstrated intense sprouting and Intussusceptive Angiogenesis. Both planar surface area (p
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Computational flow dynamics in a geometric model of Intussusceptive Angiogenesis.
Microvascular research, 2009Co-Authors: Nenad Filipovic, Akira Tsuda, Grace S. Lee, Lino F. Miele, Miao Lin, Moritz A. Konerding, Steven J. MentzerAbstract:Abstract Intussusceptive Angiogenesis is a process that forms new blood vessels by the intraluminal division of a single blood vessel into two lumens. Referred to as nonsprouting or Intussusceptive Angiogenesis, this angiogenic process has been described in morphogenesis and chronic inflammation. Mechanical forces are relevant to the structural changes associated with Intussusceptive Angiogenesis because of the growing evidence that physiologic forces influence gene transcription. To provide a detailed analysis of the spatial distribution of physiologic shear stresses, we developed a 3D finite element model of the intraluminal Intussusceptive pillar. Based on geometries observed in adult Intussusceptive Angiogenesis, physiologic shear stress distribution was studied at pillar sizes ranging from 1 to 10 μm. The wall shear stress calculations demonstrated a marked spatial dependence with discrete regions of high shear stress on the intraluminal pillar and lateral vessel wall. Furthermore, the Intussusceptive pillar created a “dead zone” of low wall shear stress between the pillar and vessel bifurcation apex. We conclude that the intraluminal flow fields demonstrate sufficient spatial resolution and dynamic range to participate in the regulation of Intussusceptive Angiogenesis.
