Increased Vascular Endothelial Growth Factor and Receptors

Feltis, Bryce; Wignarajah, D; Zheng, Ling; Ward, Chris; Reid, David W.; Harding, Richard; Walters, E. Haydn

doi:10.1164/rccm.200507-1105oc

Cited by 122 publications

(115 citation statements)

References 40 publications

Supporting

Mentioning

104

Contrasting

Unclassified

Order By: Relevance

“…VEGF, one of the major angiogenic factors secreted by EPC (68), is increased in the sputum (69 -71) and BAL fluid of individuals with asthma as compared with healthy controls (72). In this study, VEGF is also increased in the BAL of asthmatics as compared with healthy controls, supporting the concept of an angiogenic environment in the asthmatic lung.…”

Section: Discussionsupporting

confidence: 72%

Th1- and Th2-Dependent Endothelial Progenitor Cell Recruitment and Angiogenic Switch in Asthma

Asosingh

Swaidani

Aronica

et al. 2007

The Journal of Immunology

View full text Add to dashboard Cite

Increased numbers of submucosal vessels are a consistent pathologic component of asthmatic airway remodeling. However, the relationship between new vessel formation and asthmatic inflammatory response is unknown. We hypothesized that angiogenesis is a primary event during the initiation of airway inflammation and is linked to the recruitment of bone marrow-derived endothelial progenitor cells (EPC). To test this hypothesis, circulating EPC and EPC-derived endothelial cell colony formation of individuals with asthma or allergic rhinitis and health controls was evaluated. Circulating EPC were increased in asthma, highly proliferative, and exhibited enhanced incorporation into endothelial cell tubes as compared with controls. In an acute allergen challenge murine asthma model, EPC mobilization occurred within hours of challenge and mobilized EPC were selectively recruited into the challenged lungs of sensitized animals, but not into other organs. EPC recruitment was Th1 and Th2 dependent and was temporally associated with an increased microvessel density that was noted within 48 h of allergen challenge, indicating an early switch to an angiogenic lung environment. A chronic allergen challenge model provided evidence that EPC recruitment to the lung persisted and was associated with increasing microvessel density over time. Thus, a Th1- and Th2-dependent angiogenic switch with EPC mobilization, recruitment, and increased lung vessel formation occurs early but becomes a sustained and cumulative component of the allergen-induced asthmatic response.

show abstract

Section: Discussionsupporting

confidence: 72%

Th1- and Th2-Dependent Endothelial Progenitor Cell Recruitment and Angiogenic Switch in Asthma

Asosingh

Swaidani

Aronica

et al. 2007

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…[37][38][39][40] Interestingly, Ang1 and Ang2 were produced by different cellular sources-neutrophils and endothelial cells, respectively. We find this interesting because it may suggest that neutrophil Ang1 could play a role in regulating the vascular function/phenotype in various conditions of inflammation involving neutrophil influx.…”

Section: Discussionmentioning

confidence: 99%

Angiopoietin/Tie2 Signaling Transforms Capillaries into Venules Primed for Leukocyte Trafficking in Airway Inflammation

Fuxe

Lashnits

O’Brien

et al. 2010

The American Journal of Pathology

View full text Add to dashboard Cite

Vascular endothelial growth factor (VEGF) is a key angiogenic factor in tumors, but less is known about what drives vascular remodeling in inflammation,where plasma leakage and leukocyte influx are prominent features. In chronic airway inflammation in mice infected by the bacterium Mycoplasma pulmonis (M. pulmonis), the segment of the microvasculature that supports leukocyte adhesion and migration expands through remodeling of capillaries into vessels with features of venules. Here, we report that the angiopoietin/Tie2 pathway is an essential driving force for capillary remodeling into venules in M. pulmonisinfected mouse airways. Similar to M. pulmonis infection, systemic overexpression of angiopoietin-1 (Ang1) resulted in remodeling of airway capillaries into venular-like vessels that expressed venous markers like Pselectin, ICAM-1, and EphB4 and were sites of leukocyte adhesion during lipopolysaccharide-induced acute inflammation. Ang1 and Ang2 protein increased in M. pulmonis-infected mouse airways but came from different cellular sources: Ang1 was expressed in infiltrating neutrophils and Ang2 in endothelial cells. Indeed, systemic administration of soluble Tie2 inhibited capillary remodeling, induction of venous markers, and leukocyte influx in M. pulmonis-infected mouse airways. Together, these findings suggest that blockade of the Ang/ Tie2 pathway may represent a therapeutic approach in airway inflammation.

show abstract

“…27 Since its discovery, VEGF has been implicated in a wide range of inflammatory diseases, including pulmonary inflammation, such as ARDS, VILI, fibrosis, and asthma. [28][29][30][31][32] While VEGF plays a critical role in organogenesis, 33,34 its expression in lungs persists into adulthood and remains the predominant source of VEGF in adults. 35,36 Given the physiological role played by VEGF in lung maintenance and homeostasis, the involvement of VEGF in the pathogenesis of ARDS has been well investigated.…”

mentioning

confidence: 99%

Sp1‐Mediated Nonmuscle Myosin Light Chain Kinase Expression and Enhanced Activity in Vascular Endothelial Growth Factor–Induced Vascular Permeability

et al. 2015

View full text Add to dashboard Cite

Despite the important role played by the nonmuscle isoform of myosin light chain kinase (nmMLCK) in vascular barrier regulation and the implication of both nmMLCK and vascular endothelial growth factor (VEGF) in the pathogenesis of acute respiratory distress syndrome (ARDS), the role played by nmMLCK in VEGF-induced vascular permeability is poorly understood. In this study, the role played by nmMLCK in VEGF-induced vascular hyperpermeability was investigated. Human lung endothelial cell barrier integrity in response to VEGF is examined in both the absence and the presence of nmMLCK small interfering RNAs. Levels of nmMLCK messenger RNA (mRNA), protein, and promoter activity expression were monitored after VEGF stimulation in lung endothelial cells. nmMYLK promoter activity was assessed using nmMYLK promoter luciferase reporter constructs with a series of nested deletions. nmMYLK transcriptional regulation was further characterized by examination of a key transcriptional factor. nmMLCK plays an important role in VEGFinduced permeability. We found that activation of the VEGF signaling pathway in lung endothelial cells increases MYLK gene product at both mRNA and protein levels. Increased nmMLCK mRNA and protein expression is a result of increased nmMYLK promoter activity, regulated in part by binding of the Sp1 transcription factor on triggering by the VEGF signaling pathway. Taken together, these findings suggest that MYLK is an important ARDS candidate gene and a therapeutic target that is highly influenced by excessive VEGF concentrations in the inflamed lung.

show abstract

Increased Vascular Endothelial Growth Factor and Receptors

Cited by 122 publications

References 40 publications

Th1- and Th2-Dependent Endothelial Progenitor Cell Recruitment and Angiogenic Switch in Asthma

Th1- and Th2-Dependent Endothelial Progenitor Cell Recruitment and Angiogenic Switch in Asthma

Angiopoietin/Tie2 Signaling Transforms Capillaries into Venules Primed for Leukocyte Trafficking in Airway Inflammation

Sp1‐Mediated Nonmuscle Myosin Light Chain Kinase Expression and Enhanced Activity in Vascular Endothelial Growth Factor–Induced Vascular Permeability

Contact Info

Product

Resources

About