Determinants of Endothelial Cell Phenotype in Venules

Thurston, Gavin; Bałuk, Peter; McDonald, Donald M.

doi:10.1038/sj.mn.7300155

Cited by 33 publications

(36 citation statements)

References 85 publications

(127 reference statements)

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“…Venules are the primary site for plasma leakage and leukocyte trafficking in inflammation because of the fact that venous endothelial cells express receptors for inflammatory mediators that trigger endothelial gap formation 32 and cell adhesion molecules involved in leukocyte adhesion and transmigration. 33,34 Based on our results and published data showing that activating mutations in Tie2 causes inherited venous malformations 35 and that Ang1 may be specifically expressed in mesenchymal cells surrounding veins during vascular development, 36 we speculate that Ang1 may play a role in promoting venous identity.…”

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

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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.

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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

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“…Our results indicate that VEGF increased the expression of ICAM-1, VCAM-1, and E-selectin in HUVECs. Endothelial cells from different areas have different characteristics and different responses to growth factors (35,36). Thus, the expression of adhesion molecules in response to VEGF may be different between large vessel endothelial cells and microvascular endothelial cells.…”

Section: Vegf-induced Leukocyte Adhesiveness Was Correlated With Vegfmentioning

confidence: 99%

Vascular Endothelial Growth Factor Expression of Intercellular Adhesion Molecule 1 (ICAM-1), Vascular Cell Adhesion Molecule 1 (VCAM-1), and E-selectin through Nuclear Factor-κB Activation in Endothelial Cells

Kim

Moon

Kim

et al. 2001

Journal of Biological Chemistry

682

467

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“…pulmonis infection increases the expression of the leukocyte adhesion molecule P-selectin on remodeled capillaries and venules. 18 P-selectin-dependent rolling is one of the earliest observable events in the recruitment of leukocytes to inflamed tissues. 52 Our studies revealed that leukocyte adhesion to remodeled vessels occurred early in the disease in C3H mice, beginning during the period of rapid vascular remodeling and continuing thereafter.…”

Section: Change In Endothelial Cell Phenotypementioning

confidence: 99%

“…16,17 With the enlargement, endothelial cells of blood vessels in the anatomical position of capillaries acquire characteristics of venules, including leakiness, adherence of leukocytes, and expression of P-selectin and von Willebrand factor. 18 These changes in endothelial cell phenotype could be key to the rapid influx of leukocytes that follows M. pulmonis infection and initiates the tissue remodeling. 16,17 Like other chronic inflammatory conditions, M. pulmonis infection is accompanied by progressive tissue remodeling.…”

mentioning

confidence: 99%

Time Course of Endothelial Cell Proliferation and Microvascular Remodeling in Chronic Inflammation

Ezaki

Bałuk

Thurston

et al. 2001

The American Journal of Pathology

118

115

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Angiogenesis and vascular remodeling are features of many chronic inflammatory diseases. When diseases evolve slowly, the accompanying changes in the microvasculature would seem to be similarly gradual. Here we report that the rate of endothelial cell proliferation and the size of blood vessels increases rapidly after the onset of an infection that leads to chronic inflammatory airway disease. In C3H mice inoculated with Mycoplasma pulmonis, the tracheal microvasculature, made visible by perfusion of Lycopersicon esculentum lectin, rapidly enlarged from 4 to 7 days after infection and then plateaued. Diameters of arterioles, capillaries, and venules increased on average 148, 214, and 74%, respectively. Endothelial cell proliferation, measured by bromodeoxyuridine (BrdU) labeling, peaked at 5 days (18 times the pathogen-free value), declined sharply until day 9, but remained at ϳ3 times the pathogen-free value for at least 28 days. Remodeled capillaries and venules were sites of focal plasma leakage and extensive leukocyte adherence. Most systemic manifestations of the infection occurred well after the peak of endothelial proliferation, and the humoral immune response to M. pulmonis was among the latest, increasing after 14 days. These data show that endothelial cell proliferation and microvascular remodeling occur at an early stage of chronic airway disease and suggest that the vascular changes precede widespread tissue remodeling. Angiogenesis and vascular remodeling are important elements of the pathophysiology of cancer and chronic inflammatory diseases and may be essential for the persistence of these conditions. 1 The vasculature provides metabolic support for the diseased tissues and serves as the gatekeeper for incoming inflammatory cells and outgoing tumor cells that form metastases. The recognition that newly formed and remodeled vessels are different from those normally present led to the identification of probes to target diseased vessels selectively 2,3 and to the use of angiogenesis inhibitors in the treatment of cancer and chronic inflammation. 1,4 The properties and functional implications of angiogenic blood vessels have been examined in many animal models of cancer, 5-8 but less is known about the vascular changes in chronic inflammation. One might expect the microvasculature to change gradually as protracted inflammatory diseases evolve, or it could change rapidly at the beginning and drive other aspects of the disease. Yet the time course of changes in the vasculature in chronic inflammation has not been addressed systematically, in part because of limited suitable animal models.One animal model that has been useful for studying angiogenesis and vascular remodeling in chronic inflammation is the respiratory tract infection caused by Mycoplasma pulmonis in mice and rats. This infection causes severe, lifelong changes in the microvasculature of the airway mucosa, 9 -11 along with extensive tissue remodeling, leukocyte influx, epithelial and gland hyperplasia, and fibrosis in the airways and, in ...

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Determinants of Endothelial Cell Phenotype in Venules

Cited by 33 publications

References 85 publications

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

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

Vascular Endothelial Growth Factor Expression of Intercellular Adhesion Molecule 1 (ICAM-1), Vascular Cell Adhesion Molecule 1 (VCAM-1), and E-selectin through Nuclear Factor-κB Activation in Endothelial Cells

Time Course of Endothelial Cell Proliferation and Microvascular Remodeling in Chronic Inflammation

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