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Angiogenesis

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Articles 1 - 24 of 24

Full-Text Articles in Biochemistry, Biophysics, and Structural Biology

Exercise Rescues Gene Pathways Involved In Vascular Expansion And Promotes Functional Angiogenesis In Subcutaneous White Adipose Tissue, So Yun Min, Heather Learnard, Shashi Kant, Olga Gaelikman, Raziel Rojas-Rodriguez, Tiffany Desouza, Anand Desai, John F. Keaney Jr., Silvia Corvera, Siobhan M. Craige Apr 2019

Exercise Rescues Gene Pathways Involved In Vascular Expansion And Promotes Functional Angiogenesis In Subcutaneous White Adipose Tissue, So Yun Min, Heather Learnard, Shashi Kant, Olga Gaelikman, Raziel Rojas-Rodriguez, Tiffany Desouza, Anand Desai, John F. Keaney Jr., Silvia Corvera, Siobhan M. Craige

Open Access Articles

Exercise mitigates chronic diseases such as diabetes, cardiovascular diseases, and obesity; however, the molecular mechanisms governing protection from these diseases are not completely understood. Here we demonstrate that exercise rescues metabolically compromised high fat diet (HFD) fed mice, and reprograms subcutaneous white adipose tissue (scWAT). Using transcriptomic profiling, scWAT was analyzed for HFD gene expression changes that were rescued by exercise. Gene networks involved in vascularization were identified as prominent targets of exercise, which led us to investigate the vasculature architecture and endothelial phenotype. Vascular density in scWAT was found to be compromised in HFD, and exercise rescued this defect ...


The Effect Of Hemodynamic Force On The Maturation Of Blood Vessels During Embryogenesis, Rachel Lee Padget Aug 2017

The Effect Of Hemodynamic Force On The Maturation Of Blood Vessels During Embryogenesis, Rachel Lee Padget

MSU Graduate Theses

Throughout embryonic development, blood vessels are derived from endothelial cells by way of vasculogenesis. During angiogenesis, vessels remodel to form a hierarchy of large-diameter arteries that branch into small-diameter capillaries. In this maturation, vessels respond to unidentified signaling events to become surrounded with an outer layer of vascular smooth muscle cells (vSMCs). This results in arteries that have a thick vSMC layer, veins that have a thin vSMC layer, and capillaries that have a very thin or absent vSMC layer. What remains to be determined is the cause of the thicker layer of vSMCs around proximal arteries. Previous studies have ...


Anthrax, Matrix Biology, And Angiogenesis: Capillary Morphogenesis Gene 2 Mediates Activity And Uptake Of Type Iv Collagen-Derived Anti-Angiogenic Peptides, Jordan Grant Finnell Jun 2017

Anthrax, Matrix Biology, And Angiogenesis: Capillary Morphogenesis Gene 2 Mediates Activity And Uptake Of Type Iv Collagen-Derived Anti-Angiogenic Peptides, Jordan Grant Finnell

Theses and Dissertations

Capillary Morphogenesis Gene 2 (CMG2) is a type I transmembrane, integrin-like receptor. It was originally identified as one of several genes upregulated during capillary formation. It was subsequently identified as one of two physiological anthrax toxin receptors, where CMG2 serves as a cell-surface receptor for anthrax toxin and mediates entry of the toxin into cells via clathrin-dependent endocytosis. Additionally, loss-of-function mutations in CMG2 cause the genetic disorder hyaline fibromatosis syndrome (HFS), where the core symptom is dysregulation of extracellular matrix homeostasis (ECM), including excessive accumulation of proteinaceous hyaline material; HFS clearly indicates that CMG2 plays an essential function in ECM ...


Changes In Threonyl-Trna Synthetase Expression And Secretion In Response To Endoplasmic Reticulum Stress By Monensin In Ovarian Cancer Cells, Jared Louis Hammer Jan 2017

Changes In Threonyl-Trna Synthetase Expression And Secretion In Response To Endoplasmic Reticulum Stress By Monensin In Ovarian Cancer Cells, Jared Louis Hammer

Graduate College Dissertations and Theses

Aminoacyl-tRNA synthetases (ARS) are a family of enzymes that catalyze the charging of amino acids to their cognate tRNA in an aminoacylation reaction. Many members of this family have been found to have secondary functions independent of their primary aminoacylation function. Threonyl-tRNA synthetase (TARS), the ARS responsible for charging tRNA with threonine, is secreted from endothelial cells in response to both vascular endothelial growth factor (VEGF) and tumor necrosis factor-α (TNF-α), and stimulates angiogenesis and cell migration. Here we show a novel experimental approach for studying TARS secretion, and for observing the role of intracellular TARS in the endoplasmic reticulum ...


Suppression Of Ischemia In Arterial Occlusive Disease By Jnk-Promoted Native Collateral Artery Development, Kasmir Ramo, Koichi Sugamura, Siobhan M. Craige, John F. Keaney Jr., Roger J. Davis Aug 2016

Suppression Of Ischemia In Arterial Occlusive Disease By Jnk-Promoted Native Collateral Artery Development, Kasmir Ramo, Koichi Sugamura, Siobhan M. Craige, John F. Keaney Jr., Roger J. Davis

Davis Lab Publications

Arterial occlusive diseases are major causes of morbidity and mortality. Blood flow to the affected tissue must be restored quickly if viability and function are to be preserved. We report that disruption of the mixed-lineage protein kinase (MLK) - cJun NH2-terminal kinase (JNK) signaling pathway in endothelial cells causes severe blockade of blood flow and failure to recover in the murine femoral artery ligation model of hindlimb ischemia. We show that the MLK-JNK pathway is required for the formation of native collateral arteries that can restore circulation following arterial occlusion. Disruption of the MLK-JNK pathway causes decreased Dll4/Notch signaling, excessive ...


Vascular Endothelial Growth Factor-A Gene Electrotransfer Promotes Angiogenesis In A Porcine Model Of Cardiac Ischemia, Anna A. Bulysheva, Barbara Hargrave, Nina Burcus, Cathryn G. Lundberg, Len Murray, Richard Heller Aug 2016

Vascular Endothelial Growth Factor-A Gene Electrotransfer Promotes Angiogenesis In A Porcine Model Of Cardiac Ischemia, Anna A. Bulysheva, Barbara Hargrave, Nina Burcus, Cathryn G. Lundberg, Len Murray, Richard Heller

Bioelectrics Publications

This study aimed to assess safety and therapeutic potential of gene electrotransfer (GET) as a method for delivery of plasmid encoding vascular endothelial growth factor A (VEGF-A) to ischemic myocardium in a porcine model. Myocardial ischemia was induced by surgically occluding the left anterior descending coronary artery in swine. GET following plasmid encoding VEGF-A injection was performed at four sites in the ischemic region. Control groups either received injections of the plasmid without electrotransfer or injections of the saline vehicle. Animals were monitored for 7 weeks and the hearts were evaluated for angiogenesis, myocardial infarct size and left ventricular contractility ...


Epas1 Promotes Endothelial Cell Migration In An Irx3-Dependent Manner, Petrina K. Barnett May 2016

Epas1 Promotes Endothelial Cell Migration In An Irx3-Dependent Manner, Petrina K. Barnett

Electronic Theses & Dissertations Collection for Atlanta University & Clark Atlanta University

Iroquois homeobox gene 3 (Irx3) is a transcription factor belonging to the Iroquois family of homeobox genes that is expressed in the embryonic organs of multiple organisms. Although much is known about Irx3 during embryogenesis, the cross talk of expression and function of Irx3 in peripheral vascular disease (PVD) remains to be investigated. Herein, we demonstrate that Endothelial PAS Domain 1 (EPAS1), which is involved in vasculogenesis and diseases associated with hypoxia, is an upstream regulator of Irx3, and this interaction contributes to the cellular movement of human microvascular endothelial cells (HMVECs). Genetic EPAS1 loss-of-function (LOF) studies in HMVECs resulted ...


Decorin As A Multivalent Therapeutic Agent Against Cancer., Thomas Neill, Liliana Schaefer, Renato V. Iozzo Feb 2016

Decorin As A Multivalent Therapeutic Agent Against Cancer., Thomas Neill, Liliana Schaefer, Renato V. Iozzo

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Decorin is a prototypical small leucine-rich proteoglycan that epitomizes the multifunctional nature of this critical gene family. Soluble decorin engages multiple receptor tyrosine kinases within the target-rich environment of the tumor stroma and tumor parenchyma. Upon receptor binding, decorin initiates signaling pathways within endothelial cells downstream of VEGFR2 that ultimately culminate in a Peg3/Beclin 1/LC3-dependent autophagic program. Concomitant with autophagic induction, decorin blunts capillary morphogenesis and endothelial cell migration, thereby significantly compromising tumor angiogenesis. In parallel within the tumor proper, decorin binds multiple RTKs with high affinity, including Met, for a multitude of oncosuppressive functions including growth inhibition ...


A Critical Role Of Cxcr2 Pdz Motif-Mediated Interactions In Endothelial Progenitor Cell Homing And Angiogenesis, Yuning Hou Jan 2016

A Critical Role Of Cxcr2 Pdz Motif-Mediated Interactions In Endothelial Progenitor Cell Homing And Angiogenesis, Yuning Hou

Wayne State University Dissertations

Bone marrow-derived endothelial progenitor cells (EPCs) participate in postnatal vascularization in response to growth factors, cytokines, and chemokines. Chemokine receptor CXCR2 and its cognate ligands are reported to mediate EPC recruitment and angiogenesis. CXCR2 possesses a consensus PSD-95/DlgA/ZO-1 (PDZ) motif at its carboxyl terminus. The PDZ motif has been reported to regulate cellular signaling and functions. Here we investigated the potential role of the PDZ motif in CXCR2-mediated EPC motility and angiogenesis. We have found that introducing exogenous CXCR2 C-terminus significantly attenuated in vitro EPC migration and angiogenic activities in response to CXCR2 ligands, as well as in ...


Characterization Of A Non-Canonical Function For Threonyl-Trna Synthetase In Angiogenesis, Adam Christopher Mirando Jan 2015

Characterization Of A Non-Canonical Function For Threonyl-Trna Synthetase In Angiogenesis, Adam Christopher Mirando

Graduate College Dissertations and Theses

In addition to its canonical role in aminoacylation, threonyl-tRNA synthetase (TARS) possesses pro-angiogenic activity that is susceptible to the TARS-specific antibiotic borrelidin. However, the therapeutic benefit of borrelidin is offset by its strong toxicity to living cells. The removal of a single methylene group from the parent borrelidin generates BC194, a modified compound with significantly reduced toxicity but comparable anti-angiogenic potential. Biochemical analyses revealed that the difference in toxicities was due to borrelidin's stimulation of amino acid starvation at ten-fold lower concentrations than BC194. However, both compounds were found to inhibit in vitro and in vivo models of angiogenesis ...


Mapping The Human Vasculature By In Vivo Phage Display, Julianna Bronk Aug 2014

Mapping The Human Vasculature By In Vivo Phage Display, Julianna Bronk

UT GSBS Dissertations and Theses (Open Access)

In vivo phage display screenings by intravenous injection of a random phage-displayed peptide library allow for the selection of peptides that localize to specific vascular beds. At the University of Texas MD Anderson Cancer Center, we have had the opportunity to perform phage display screenings in cancer patients in order to select for cancer specific targets directly in humans. These targets serve to define biochemical diversity of endothelial cell surfaces and can be validated and explored towards the design of vascular-targeted pharmacology. In the most recent patient screen, samples were recovered from hepatocellular carcinoma (HCC) as well as 26 additional ...


Molecular Mechanisms Of Neuropilin-Ligand Binding, Matthew W. Parker Jan 2014

Molecular Mechanisms Of Neuropilin-Ligand Binding, Matthew W. Parker

Theses and Dissertations--Molecular and Cellular Biochemistry

Neuropilin (Nrp) is an essential cell surface receptor with dual functionality in the cardiovascular and nervous systems. The first identified Nrp-ligand family was the Semaphorin-3 (Sema3) family of axon repulsion molecules. Subsequently, Nrp was found to serve as a receptor for the vascular endothelial growth factor (VEGF) family of pro-angiogenic cytokines. In addition to its physiological role, VEGF signaling via Nrp directly contributes to cancer stemness, growth, and metastasis. Thus, the Nrp/VEGF signaling axis is a promising anti-cancer therapeutic target. Interestingly, it has recently been shown that Sema3 and VEGF are functionally opposed to one another, with Sema3 possessing ...


The Role Of Ykl-40 In The Progression Of Glioblastoma, Ralph Anthony Francescone Sep 2013

The Role Of Ykl-40 In The Progression Of Glioblastoma, Ralph Anthony Francescone

Open Access Dissertations

Glioblastoma Multiforme (GBM) is the most common brain cancer and one of the most fatal forms of cancer overall. The average survival time is 10-14 months, and less than 10% of patients survive more than 5 years after diagnosis. It is characterized by extreme vasculature, chemo/radioresistance, and invasiveness into the normal brain. The current standard of care, which includes surgical removal of tumor, radiation, and the chemotherapeutic agent temozolomide, initially stunt tumor growth. Nevertheless, the tumor invariably rebounds and the patient succumbs to the disease. Therefore, there is an urgent need to develop new therapies for this devastating disease ...


The Creation Of Α2nc1 Transgenic Drosophila Melanogaster, Jordan Olberding Aug 2013

The Creation Of Α2nc1 Transgenic Drosophila Melanogaster, Jordan Olberding

Honors College Capstone Experience/Thesis Projects

The α2 isoform of collagen IV’s noncollagenous 1 domain (α2NC1 or canstatin) has shown promise as an anti-cancer molecule, possessing both angiostatic and pro-apoptotic properties. This work aims to further the knowledge of α2NC1 by conducting a truly in vivo study in which the Gal4-induced endogenous overexpression of α2NC1 in Drosophila melanogaster will be used to assess the effects of α2NC1 upon normal development as well as tumorigenesis. To this end, transgenic fly lines capable of overexpressing α2NC1 were created. Initial overexpression studies indicated no developmental phenotype was caused by abundance of α2NC1. However, future overexpression studies in which ...


Cerium Oxide Nanoparticles Sensitize Pancreatic Cancer Cells To Radiation By Promoting Acidic Ph, Ros, And Jnk Dependent Apoptosis, Melissa Wason Jan 2013

Cerium Oxide Nanoparticles Sensitize Pancreatic Cancer Cells To Radiation By Promoting Acidic Ph, Ros, And Jnk Dependent Apoptosis, Melissa Wason

Electronic Theses and Dissertations

Side effects of radiation therapy (RT) remain the most challenging issue for pancreatic cancer treatment. In this report we determined whether and how cerium oxide nanoparticles (CONPs) sensitize pancreatic cancer cells to RT. CONP pretreatment enhanced radiation-induced reactive oxygen species (ROS) production preferentially in acidic cell-free solutions as well as acidic human pancreatic cancer cells. In acidic environments, CONPs favor the scavenging of superoxide radical over the hydroxyl peroxide resulting in accumulation of the latter whereas in neutral pH CONPs scavenge both. CONP treatment prior to RT markedly potentiated the cancer cell apoptosis both in culture and in tumors and ...


Development Of A Protocol To Measure Gene Expression In The Mouse Tibia, Daniel Hoover Jun 2012

Development Of A Protocol To Measure Gene Expression In The Mouse Tibia, Daniel Hoover

Biomedical Engineering

Numerous molecular factors active in bone tissue direct fracture repair and remodeling which can be altered by disease conditions such as Peripheral Arterial Disease (PAD) and Osteoporosis. Methods of molecular biology are commonly applied to investigate the expression and role of these molecular factors. This project presents a robust three-step protocol for examining gene expression in the mouse tibia. The protocol begins with isolating RNA from a flash frozen tibia sample. The isolated RNA is reverse transcribed into cDNA. Finally, PCR is performed to indentify expressed genes. Establishing this protocol will allow further research into the mechanisms of bone remodeling ...


The Haptotactic Motility Of Angiogenic Endothelial Cells, Breana E. Bennett May 2012

The Haptotactic Motility Of Angiogenic Endothelial Cells, Breana E. Bennett

Honors College

Angiogenesis, an essential but often pathological biological process, requires complex cellular coordination. This coordination is achieved through numerous extracellular signals. We investigated the role of the extracellular matrix (ECM) protein fibronectin in the support of angiogenesis and endothelial cell motility. The directed migration in response to increasing concentration of ECM proteins is termed haptotaxis. We created a preliminary, two-dimensional model of the haptotactic motility of endothelial cells using a step change in fibronectin density as a substrate. Bovine aortic endothelial cells (BAECs) exhibited directional motility towards the higher fibronectin concentration side. In addition, the physical and mechanical properties of BAECs ...


Molecular Mechanisms Involved In Inflammatory Angiogenesis Induced By Monocyte Chemotactic Protein Induced Protein-1 (Mcpip1), Arpita Roy Jan 2012

Molecular Mechanisms Involved In Inflammatory Angiogenesis Induced By Monocyte Chemotactic Protein Induced Protein-1 (Mcpip1), Arpita Roy

Electronic Theses and Dissertations

Major diseases such as cardiovascular diseases, diabetes, obesity and tumor growth are known to involve inflammatory angiogenesis. MCP-induced protein 1 (MCPIP1) encoded by ZC3H12A gene, was reported to promote angiogenesis and is addressed in my dissertation as MCPIP. The mechanism/s involved in the angiogenic differentiation induced by MCPIP was however unknown. The aim of this study was to bridge this gap in our knowledge and delineate the molecular mechanisms and sequential processes involved in angiogenesis mediated via MCPIP. To determine if angiogenesis induced by inflammatory cytokines, TNF-, IL-1 and IL-8 is mediated via induction of MCPIP, knockdown of MCPIP ...


Characterizing The Phosphorylation State Of Tie2 Using Sh2 Domain Fusion Proteins, Kenneth Yuth Dec 2011

Characterizing The Phosphorylation State Of Tie2 Using Sh2 Domain Fusion Proteins, Kenneth Yuth

Theses and Dissertations

The cardiovascular system develops through two distinct processes in embryogenesis: vasculogenesis, whereby the primary plexus in the heart is formed along with embryonic and extraembryonic vasculature, and angiogenesis, which begins after vasculogenesis and results in the refinement and maturation of the branched vessel system. In pathological angiogenesis, tumors expand by releasing pro-angiogenic factors in response to hypoxic conditions. The Tie receptors, Tie1 and Tie2, are receptor tyrosine kinases that are integral to angiogenic pathways. A family of Angiopoietins, Ang1-4, have been shown to act as ligands for Tie2, of which Ang1 and Ang2 are best characterized. Activation of the receptor ...


Phosphodiesterase-5 Inhibition: A Novel Strategy To Improve Stem Cell Therapy In The Heart, Nicholas Hoke Jan 2011

Phosphodiesterase-5 Inhibition: A Novel Strategy To Improve Stem Cell Therapy In The Heart, Nicholas Hoke

Theses and Dissertations

Several studies have shown cellular replacement therapy as a treatment strategy of myocardial infarction but results have been limited. Therefore, enhancing the therapeutic potential of stem cells injected into ischemic microenvironments by novel preconditioning (PC) techniques is critical for improving cellular therapy. Recent studies have shown that inhibition of phosphodiesterase-5 (PDE-5) is a powerful strategy to precondition the heart and cardiomyocytes against ischemia/reperfusion injury. We therefore tested the hypothesis that inhibition of PDE-5 with sildenafil (Viagra®) or selective knockdown with a silencing vector in adipose derived stem cells (ASCs) would improve their survival after ischemia/reoxygenation in vitro and ...


A Mathematical Model For The Role Of Cell Signal Transduction In The Initiation And Inhibition Of Angiogenesis, Howard Levine, Anna L. Tucker, Marit Nilsen-Hamilton Jun 2009

A Mathematical Model For The Role Of Cell Signal Transduction In The Initiation And Inhibition Of Angiogenesis, Howard Levine, Anna L. Tucker, Marit Nilsen-Hamilton

Mathematics Publications

Neovascular formation can be divided into three main stages (which may be overlapping): (1) changes within the existing vessel, (2) formation of a new channel, (3) maturation of the new vessel. In two previous papers, [Levine, H.A. and Sleeman, B.D. (1997) "A system of reaction diffusion equations arising in the theory of reinforced random walks" SIAM J. Appl. Math. 683-730; Levine, H.A., Sleeman, B.D. and Nilsen-Hamilton, M. (2001b) "Mathematical modelling of the onset of capillary formation initiating angiogenesis." J. Math. Biol. 195-238] the authors introduced a new approach to angiogenesis, based on the theory of reinforced ...


Characterization Of Heat Shock Protein A12b As A Novel Angiogenesis Regulator., Rebecca J. Steagall Aug 2008

Characterization Of Heat Shock Protein A12b As A Novel Angiogenesis Regulator., Rebecca J. Steagall

Electronic Theses and Dissertations

Previously, we cloned Heat shock protein A12B (HspA12B), the newest member of a recently defined subfamily of proteins distantly related to the Hsp70 family that are enriched in atherosclerotic lesions. We have found that HspA12B is predominantly expressed in vascular endothelium, and that it is involved in angiogenesis which we probed by in vitro angiogenesis assays (Matrigel), migration assays and Directed In Vivo Angiogenesis Assay (DIVAA). Hsp70s are molecular chaperones that are inducible by stress and have been found to be anti-apoptotic (Li et al. 2000; Nylandsted et al. 2000; Garrido et al. 2001). Because of its homology to Hsp70 ...


Mathematical Modeling Of The Onset Of Capillary Formation Initiating Angiogenesis, Howard Levine, Brian D. Sleeman, Marit Nilsen-Hamilton Mar 2001

Mathematical Modeling Of The Onset Of Capillary Formation Initiating Angiogenesis, Howard Levine, Brian D. Sleeman, Marit Nilsen-Hamilton

Mathematics Publications

It is well accepted that neo-vascular formation can be divided into three main stages (which may be overlapping): (1) changes within the existing vessel, (2) formation of a new channel, (3) maturation of the new vessel.

In this paper we present a new approach to angiogenesis, based on the theory of reinforced random walks, coupled with a Michaelis-Menten type mechanism which views the endothelial cell receptors as the catalyst for transforming angiogenic factor into proteolytic enzyme in order to model the first stage. In this model, a single layer of endothelial cells is separated by a vascular wall from an ...


Xenopus Laevis Gelatinase B (Xmmp-9): Development, Regeneration, And Wound Healing, Brian Walter, Maria Carinato, Jonathan Henry Mar 2000

Xenopus Laevis Gelatinase B (Xmmp-9): Development, Regeneration, And Wound Healing, Brian Walter, Maria Carinato, Jonathan Henry

Brian Walter

It has been argued that matrix metalloproteinases play important roles in cellular differentiation and regeneration in certain systems. While studying changes in gene expression associated with the phenomena of cornea/lens transdifferentiation ("lens regeneration"), which takes place in the larva of Xenopus laevis, we identified the Xenopus gelatinase B gene. The open reading frame is homologous to other gelatinase B genes identified in other species and encodes all of the domains characteristic of this protein. Xenopus gelatinase B (Xmmp-9) is first expressed during early tail-bud stages in a subset of mesodermal cells scattered throughout the body. Expression is also seen ...