Pericyte endothelial gap junctions in human cerebral capillaries

Cuevas, Pedro; Gutiérrez-Díaz, José A.; Reimers, Diana; Dujovny, Manuel; Díaz, Fernando G.; Ausman, James I.

doi:10.1007/bf00319000

Cited by 129 publications

(73 citation statements)

References 23 publications

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“…15 Pericytes wrap around endothelial cells and play an essential role in stabilization and hemodynamic functions of blood vessels. 16,17 In contrast, tumor vessels have multiple morphological abnormalities and are often leaky and hemorrhagic, in part due to overproduction of VEGF. 18 Tumor vessel walls are thin, probably due to abnormalities in pericytes and other supporting cells.…”

Section: Introductionmentioning

confidence: 99%

Impact of vessel maturation on antiangiogenic therapy in ovarian cancer

Lü

Thaker

Lin

et al. 2008

American Journal of Obstetrics and Gynecology

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Condensation-Pericytes contribute to endothelial survival in tumor vasculature and represent a potential therapeutic target.Objective-To examine the functional and therapeutic significance of pericytes in ovarian cancer vasculature.Study Design-Tumor vessel morphology and efficacy of endothelial and pericyte targeting were examined using in vivo ovarian cancer models. The expression of platelet derived growth factor (PDGF) ligands and receptors was examined in endothelial, pericyte-like, and ovarian cancer cells.Results-Relative to normal vessels, tumor vasculature was characterized by loosely attached pericytes in reduced density. PDGF-BB was expressed predominantly by the endothelial and cancer cells whereas PDGFRβ was present in pericyte-like cells. PDGF-BB significantly increased migration of and VEGF production by pericyte-like cells while PDGFRβ blockade abrogated these effects. Dual VEGF (VEGF-Trap) and PDGF-B (PDGF-Trap) targeted therapy was more effective in inhibiting in vivo tumor growth than either agent alone.Conclusions-Aberrations in the tumor microenvironment contribute to endothelial cell survival. Strategies targeting both endothelial cells and pericytes should be considered for clinical trials.

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Section: Introductionmentioning

confidence: 99%

Impact of vessel maturation on antiangiogenic therapy in ovarian cancer

Lü

Thaker

Lin

et al. 2008

American Journal of Obstetrics and Gynecology

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“…The processes do form cellular adhesions with the endothelium at discrete points, described as peg-and-socket junctions, and are mediated by the adhesion molecule N-cadherin (Gerhardt et al 2000). In addition, other pericyte-endothelial cellular adhesions have been identified including adhesion plaques, gap junctions, and tight junctions (Courtoy and Boyles 1983;Cuevas et al 1984;Larson et al 1987;Diaz-Flores et al 2009). CNS PCs have been shown to have unique properties compared to PCs in other tissues.…”

Section: Mural Cellsmentioning

confidence: 99%

The Blood–Brain Barrier

Daneman

Prat

2015

Cold Spring Harb Perspect Biol

2,555

1,829

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Blood vessels are critical to deliver oxygen and nutrients to all of the tissues and organs throughout the body. The blood vessels that vascularize the central nervous system (CNS) possess unique properties, termed the blood-brain barrier, which allow these vessels to tightly regulate the movement of ions, molecules, and cells between the blood and the brain. This precise control of CNS homeostasis allows for proper neuronal function and also protects the neural tissue from toxins and pathogens, and alterations of these barrier properties are an important component of pathology and progression of different neurological diseases. The physiological barrier is coordinated by a series of physical, transport, and metabolic properties possessed by the endothelial cells (ECs) that form the walls of the blood vessels, and these properties are regulated by interactions with different vascular, immune, and neural cells. Understanding how these different cell populations interact to regulate the barrier properties is essential for understanding how the brain functions during health and disease.

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“…Pericytes are embedded into the vascular basement membrane and make direct contact with endothelial cells through extensions that reach deeply into the endothelial cells, without an intervening basal membrane. 1,2 Endothelial cells are better characterized, but pericytes are emerging as critical regulators of vascular function because they are thought to stabilize the vessel wall and to regulate endothelial cell survival, growth, maturation, and permeability. 2 Pericytes have multilineage progenitor potential and are developmentally close to mesenchymal stem cells (MSCs).…”

Section: Introductionmentioning

confidence: 99%

EphrinB reverse signaling contributes to endothelial and mural cell assembly into vascular structures

Salvucci

Maric

Economopoulou

et al. 2009

Blood

121

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EphrinB transmembrane ligands and their cognate EphB receptor tyrosine kinases regulate vascular development through bidirectional cell-to-cell signaling, but little is known about the role of EphrinB during postnatal vascular remodeling. We report that EphrinB is a critical mediator of postnatal pericyte-to-endothelial cell assembly into vascular structures. This function is dependent upon extracellular matrixsupported cell-to-cell contact, engagement of EphrinB by EphB receptors expressed on another cell, and Srcdependent phosphorylation of the intracytoplasmic domain of EphrinB. Phosphorylated EphrinB marks angiogenic blood vessels in the developing and hypoxic retina, the wounded skin, and tumor tissue, and is detected at contact points between endothelial cells and pericytes. Furthermore, inhibition of EphrinB activity prevents proper assembly of pericytes and endothelial cells into vascular structures. These results reveal a role for EphrinB signaling in orchestrating pericyte/endothelial cell assembly, and suggest that therapeutic targeting of EphrinB may prove useful for disrupting angiogenesis when it contributes to disease. (Blood. 2009;114:1707-1716) IntroductionBlood vessels are composed of endothelial cells that form the inner lining of vessels and pericytes, also known as mural cells, that envelope the endothelium. Pericytes are embedded into the vascular basement membrane and make direct contact with endothelial cells through extensions that reach deeply into the endothelial cells, without an intervening basal membrane. 1,2 Endothelial cells are better characterized, but pericytes are emerging as critical regulators of vascular function because they are thought to stabilize the vessel wall and to regulate endothelial cell survival, growth, maturation, and permeability. 2 Pericytes have multilineage progenitor potential and are developmentally close to mesenchymal stem cells (MSCs). 3 Genetic mouse models have implicated several receptor-ligand systems as mediators of endothelial-pericyte interactions, including Ang-1/Tie2, transforming growth factor-␤ and its receptors, plateletderived growth factor (PDGF)/PDGF receptor-1, the sphingosine-1-phosphate (S1P)/S1P 1 , and Dll4/Notch. 2 The family of EphB (erythropoietin-producing hepatoma) receptors tyrosine kinases and their surface-bound EphrinB (erythropoietin-producing hepatoma interactor B) ligands have recently emerged as critical regulators of cardiovascular development and pathologic angiogenesis, modulating both endothelial cells and pericyte function. 4 Upon cell-to-cell contact, EphrinB ligands both activate the cognate EphB receptors (forward signaling) and undergo phosphorylation at the C terminus initiating signaling (reverse signaling). 5,6 Genetic experiments have shown that the global knockout of EphB4, EphrinB2, or the endothelial-specific inactivation of EphrinB2 produced a very similar phenotype of embryonic death with prominent remodeling defects of the vascular system. [7][8][9] The role of EphrinB2 reverse signaling in vascular ...

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Pericyte endothelial gap junctions in human cerebral capillaries

Cited by 129 publications

References 23 publications

Impact of vessel maturation on antiangiogenic therapy in ovarian cancer

Impact of vessel maturation on antiangiogenic therapy in ovarian cancer

The Blood–Brain Barrier

EphrinB reverse signaling contributes to endothelial and mural cell assembly into vascular structures

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