MS127 EXPRESSIONS OF MACROPHAGE METALLOELASTASE (MMP-12) IN EXTRACELLULAR MATRIX OF ATHEROSCLEROTIC TISSUES FOLLOWING DISRUPTION OF THE VASCULAR ENDOTHELIAL SURFACE

2010 ◽  
Vol 11 (2) ◽  
pp. 135
Author(s):  
M. Mustakim ◽  
G.A. Froemming ◽  
M.S. Abdul Rahman ◽  
H. Nawawi ◽  
N. Ismail ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Vascular Endothelial ◽  
Endothelial Surface

scholarly journals VEGF145, a Secreted Vascular Endothelial Growth Factor Isoform That Binds to Extracellular Matrix

1997 ◽  
Vol 272 (11) ◽  
pp. 7151-7158 ◽  
Author(s):  
Zoya Poltorak ◽  
Tzafra Cohen ◽  
Revital Sivan ◽  
Yelena Kandelis ◽  
Gadi Spira ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Vascular Endothelial ◽  
Endothelial Growth Factor

Connective tissue growth factor and vascular endothelial growth factor from airway smooth muscle interact with the extracellular matrix

2006 ◽  
Vol 290 (1) ◽  
pp. L153-L161 ◽  
Author(s):  
Janette K. Burgess ◽  
Qi Ge ◽  
Maree H. Poniris ◽  
Sarah Boustany ◽  
Stephen M. Twigg ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Vascular Endothelial Growth Factor ◽  
Smooth Muscle ◽  
Growth Factor ◽  
Connective Tissue ◽  
Airway Smooth Muscle ◽  
Connective Tissue Growth Factor ◽  
Tissue Growth ◽  
Vascular Endothelial ◽  
Endothelial Growth Factor

Airway remodeling describes the structural changes that occur in the asthmatic airway that include airway smooth muscle hyperplasia, increases in vascularity due to angiogenesis, and thickening of the basement membrane. Our aim in this study was to examine the effect of transforming growth factor-β on the release of connective tissue growth factor and vascular endothelial growth factor from human airway smooth muscle cells derived from asthmatic and nonasthmatic patients. In addition we studied the immunohistochemical localization of these cytokines in the extracellular matrix after stimulating bronchial rings with transforming growth factor-β. Connective tissue growth factor and vascular endothelial growth factor were released from both cell types and colocalized in the surrounding extracellular matrix. Prostaglandin E2 inhibited the increase in connective tissue growth factor mRNA but augmented the release of vascular endothelial growth factor. Matrix metalloproteinase-2 decreased the amount of connective tissue growth factor and vascular endothelial growth factor, but not fibronectin deposited in the extracellular matrix. This report provides the first evidence that connective tissue growth factor may anchor vascular endothelial growth factor to the extracellular matrix and that this deposition is decreased by matrix metalloproteinase-2 and prostaglandin E2. This relationship has the potential to contribute to the changes that constitute airway remodeling, therefore providing a novel focus for therapeutic intervention in asthma.

Vascular endothelial growth factor-induced secretion of fibronectin is ERK dependent

2004 ◽  
Vol 286 (3) ◽  
pp. L539-L545 ◽  
Author(s):  
Altaf S. Kazi ◽  
Shidan Lotfi ◽  
Elena A. Goncharova ◽  
Omar Tliba ◽  
Yassine Amrani ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Vascular Endothelial Growth Factor ◽  
Smooth Muscle ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Airway Remodeling ◽  
Vegf Receptor ◽  
Vascular Endothelial ◽  
Matrix Deposition ◽  
Endothelial Growth Factor

In severe asthma, cytokines and growth factors contribute to the proliferation of smooth muscle cells and blood vessels, and to the increased extracellular matrix deposition that constitutes the process of airway remodeling. Vascular endothelial growth factor (VEGF), which regulates vascular permeability and angiogenesis, also modulates the function of nonendothelial cell types. In this study, we demonstrate that VEGF induces fibronectin secretion by human airway smooth muscle (ASM) cells. In addition, stimulation of ASM with VEGF activates ERK, but not p38MAPK, and fibronectin secretion is ERK dependent. Both ERK activation and fibronectin secretion appear to be mediated through the VEGF receptor flt-1, as evidenced by the effects of the flt-1-specific ligand placenta growth factor. Finally, we demonstrate that ASM cells constitutively secrete VEGF, which is increased in response to PDGF, transforming growth factor-β, IL-1β, and PGE2. We conclude that ASM-derived VEGF, through modulation of the extracellular matrix, may play an important role in airway remodeling seen in asthma.

scholarly journals The vascular endothelial growth factor (VEGF) isoforms: differential deposition into the subepithelial extracellular matrix and bioactivity of extracellular matrix-bound VEGF.

1993 ◽  
Vol 4 (12) ◽  
pp. 1317-1326 ◽  
Author(s):  
J E Park ◽  
G A Keller ◽  
N Ferrara
Keyword(s):  
Extracellular Matrix ◽  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Vascular Endothelial ◽  
Vegf Mrna ◽  
Angiogenic Potential ◽  
Molecular Masses ◽  
Matrix Bound ◽  
Endothelial Growth Factor ◽  
Vegf Isoforms

Vascular endothelial growth factor (VEGF)mRNA undergoes alternative splicing events that generate four different homodimeric isoforms, VEGF121, VEGF165, VEGF189, or VEGF206. VEGF121 is a nonheparin-binding acidic protein, which is freely diffusible. The longer forms, VEGF189 or VEGF206, are highly basic proteins tightly bound to extracellular heparin-containing proteoglycans. VEGF165 has intermediate properties. To determine the localization of VEGF isoforms, transfected human embryonic kidney CEN4 cells expressing VEGF165, VEGF189, or VEGF206 were stained by immunofluorescence with a specific monoclonal antibody. The staining was found in patches and streaks suggestive of extracellular matrix (ECM). VEGF165 was observed largely in Golgi apparatus-like structures. Immunogold labeling of cells expressing VEGF189 or VEGF206 revealed that the staining was localized to the subepithelial ECM. VEGF associated with the ECM was bioactive, because endothelial cells cultured on ECM derived from cells expressing VEGF189 or VEGF206 were markedly stimulated to proliferate. In addition, ECM-bound VEGF can be released into a soluble and bioactive form by heparin or plasmin. ECM-bound VEGF189 and VEGF206 have molecular masses consistent with the intact polypeptides. The ECM may represent an important source of VEGF and angiogenic potential.

Abstract 326: Granzyme B Releases Vascular Endothelial Growth Factor from Extracellular Matrix Stores and Induces Vascular Permeability in vivo

2013 ◽  
Vol 33 (suppl_1) ◽  
Author(s):  
Alon Hendel ◽  
David J Granville
Keyword(s):  
Extracellular Matrix ◽  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Vascular Permeability ◽  
Chronic Inflammation ◽  
Granzyme B ◽  
Vascular Endothelial ◽  
Endothelial Growth Factor ◽  
Vegf Release

Introduction The formation of unstable and leaky neovessels underlies the pathogenesis of a large number of chronic inflammatory diseases. Granzyme B (GZMB) is a serine protease that is expressed and released by a variety of immune cells and accumulates in the extracellular matrix (ECM) during chronic inflammation where it cleaves a number of ECM proteins, including fibronectin (FN). Vascular endothelial growth factor (VEGF) is a potent vascular permeabilizing agent that is sequestered in the ECM by binding FN in both normal and diseased tissue. We hypothesize that GZMB cleavage of FN will release VEGF from its extracellular stores and promote vascular permeability as a mechanism that contributes to neovessel leakage during chronic inflammation. Methods GZMB-mediated VEGF release from either FN coated wells or endogenously produce endothelial cell (EC) matrix was measured by VEGF ELISA. VEGF-release supernatants were used to treat EC and VEGF receptor 2 (VEGFR2) activation was evaluated by immunoblotting for phosphorylated VEGFR2. Evan’s blue was injected intravenously to CD1 mice followed by ear injection of either mouse GZMB, saline control, GZMB + neutralizing mouse VEGF antibody or GZMB+ IgG control (n=5 for each experimental group). Vascular leakage was evaluated by Evan’s blue dye extraction. Results GZMB effectively releases VEGF from both FN and from EC matrix, while inhibition of GZMB prevented VEGF release. GZMB-mediated VEGF release resulted in significant activation of VEGFR2 in EC monolayer signified by increased VEGFR2 phosphorylation. GZMB ear injection resulted in a significant increase in vascular permeability in vivo. Importantly, co-injection of GZMB and neutralizing mouse VEGF antibody significantly reduced vascular leakage compared to co-injection of GZMB and matching IgG control. Conclusions and Impact GZMB increases VEGF bioavailability by releasing it from the ECM leading to VEGFR2 activation and increased vascular permeability in vivo. These findings present a novel role for GZMB as a modulator of vascular response during chronic inflammation.

Interaction between vascular endothelial cells and vascular intimal spindle-shaped cells in vitro

1983 ◽  
Vol 60 (1) ◽  
pp. 89-102
Author(s):  
D de Bono ◽  
C. Green
Keyword(s):  
Extracellular Matrix ◽  
Endothelial Cells ◽  
Vascular Endothelial Cells ◽  
Three Dimensional ◽  
Vascular Endothelial ◽  
Pure Cultures ◽  
Species Specific ◽  
Endothelial Growth Factor

The interactions between human or bovine vascular endothelial cells and fibroblast-like vascular intimal spindle-shaped cells have been studied in vitro, using species-specific antibodies to identify the different components in mixed cultures. Pure cultures of endothelial cells grow as uniform, nonoverlapping monolayers, but this growth pattern is lost after the addition of spindle cells, probably because the extracellular matrix secreted by the latter causes the endothelial cells to modify the way they are attached to the substrate. The result is a network of tubular aggregates of endothelial cells in a three-dimensional ‘polylayer’ of spindle-shaped cells. On the other hand, endothelial cells added to growth-inhibited cultures of spindle-shaped cells will grow in sheets over the surface of the culture. Human endothelial cells grown in contact with spindle-shaped cells have a reduced requirement for a brain-derived endothelial growth factor. The interactions of endothelial cells and other connective tissue cells in vitro may be relevant to the mechanisms of endothelial growth and blood vessel formation in vivo, and emphasize the potential importance of extracellular matrix in controlling endothelial cell behaviour.

Three-Dimensional Simulation of In Vitro Angiogenesis: Effects of Extracellular Matrix Structure and Density

2010 ◽  
Author(s):  
Lowell Taylor Edgar ◽  
James E. Guilkey ◽  
Clayton J. Underwood ◽  
Brenda Baggett ◽  
Urs Utzinger ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Endothelial Cells ◽  
Three Dimensional ◽  
Vascular Endothelial ◽  
Chemical Factors ◽  
Dimensional Simulation ◽  
Endothelial Growth Factor ◽  
In Vitro Angiogenesis

The process of angiogenesis is regulated by both chemical and mechanical signaling. While the role of chemical factors such as vascular endothelial growth factor (VEGF) during angiogenesis has been extensively studied, the influence of the mechanostructural environment on new vessel generation has received significantly less attention. During angiogenesis, endothelial cells in the existing vasculature detach and migrate out into the surrounding extracellular matrix (ECM), forming tubular structures that eventually mature into new blood vessels. This process is modulated by the structure and composition of the ECM [1]. The ECM is then remodeled by endothelial cells in the elongating neovessel tip, resulting in matrix condensation and changes in fiber orientation [2]. The mechanism as to how angiogenic vasculature and the ECM influence each other is poorly understood.

scholarly journals Extracellular Matrix–Associated Factors Play Critical Roles in Regulating Pancreatic β-Cell Proliferation and Survival

Endocrinology ◽  
2019 ◽  
Vol 160 (8) ◽  
pp. 1885-1894 ◽  
Author(s):  
Shannon E Townsend ◽  
Maureen Gannon
Keyword(s):  
Extracellular Matrix ◽  
Cell Proliferation ◽  
Cell Mass ◽  
Vascular Endothelial ◽  
Β Cells ◽  
Β Cell ◽  
Cellular Communication Network ◽  
Treatment Of Diabetes ◽  
Specific Receptors ◽  
Endothelial Growth Factor

Abstract This review describes formation of the islet basement membrane and the function of extracellular matrix (ECM) components in β-cell proliferation and survival. Implications for islet transplantation are discussed. The insulin-producing β-cell is key for maintaining glucose homeostasis. The islet microenvironment greatly influences β-cell survival and proliferation. Within the islet, β-cells contact the ECM, which is deposited primarily by intraislet endothelial cells, and this interaction has been shown to modulate proliferation and survival. ECM-localized growth factors, such as vascular endothelial growth factor and cellular communication network 2, signal through specific receptors and integrins on the β-cell surface. Further understanding of how the ECM functions to influence β-cell proliferation and survival will provide targets for enhancing functional β-cell mass for the treatment of diabetes.

scholarly journals Intense remodeling of extracellular matrix within the varicose vein: the role of gelatinases and vascular endothelial growth factor

2020 ◽  
Author(s):  
Anna Horecka ◽  
Anna Hordyjewska ◽  
Jadwiga Biernacka ◽  
Wojciech Dąbrowski ◽  
Tomasz Zubilewicz ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Varicose Veins ◽  
Artery Bypass ◽  
Bypass Graft ◽  
Clinical State ◽  
Vascular Endothelial ◽  
Altered Expression ◽  
Endothelial Growth Factor

Abstract Background Increased blood pressure in the varicose veins (VV) can contribute to the overexpression of matrix metalloproteinases (MMPs), affecting the endothelium, smooth muscle, and extracellular matrix of the vein wall. Gelatinases (MMP-2 and MMP-9), hypoxia, and inflammation occurring in the VV wall contribute to the increased expression of vascular endothelial growth factor (VEGF). Aims Our objective was to analyze the concentration of gelatinases and VEGF in the great saphenous VV wall and plasma of patients. Methods In total, 65 patients (2nd degree according to clinical state classification, etiology, anatomy, and pathophysiology—CEAP classification) aged 22 to 70 were enrolled. Control veins (n = 10) were collected from the patients who underwent coronary artery bypass graft surgery. Control plasma (n = 20) was obtained from healthy individuals. Gelatinases and VEGF levels were measured with the usage of ELISA method. Results A significant increase in MMP-9 (11.2 vs. 9.98 ng/mg of protein) and VEGF (41.06 vs. 26 ng/g of protein) concentration in VV wall compared with control veins was observed. A positive correlation between VEGF versus MMP-2 (p = 0.03, r = 0.27) was found in the VV wall. However, no correlation was found between the concentration of VEGF and MMP-9 (p = 0.4, r = 0.11) in the VV wall. In addition, no statistical differences between MMP-9, MMP-2, and VEGF levels in plasma of VV patients compared with controls were noticed. Conclusions The results of the present study confirm that VV’s patients have altered expression of MMPs and VEGF. Overexpression of MMP-9 and VEGF in the VV wall may contribute to the spreading of inflammatory process and suggests the intense remodeling of extracellular tissue within the VV wall.

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