Comparative gene expression profiling of human umbilical vein endothelial cells and ocular vascular endothelial cells

Browning, Andrew C.; Halligan, Eugene; Stewart, Elizabeth A.; Swan, Daniel; Dove, Rosamund; Samaranayake, Govindi J.; Amoaku, Winfried

doi:10.1136/bjophthalmol-2011-300572

Cited by 39 publications

(39 citation statements)

References 24 publications

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“…HUVEC or bovine pulmonary arterial EC [19, 20, 22]. Conflicting results may simply reflect different characteristics of EC from macro- and microvascular vessels defined by their varying gene expression profiles, which even differ between microvascular EC of the retina and the choroid [52]. …”

Section: Discussionmentioning

confidence: 99%

Inhibition of Single Routes of Intracellular Signaling is Not Sufficient to Neutralize the Biphasic Disturbance of a Retinal Endothelial Cell Barrier Induced by VEGF-A165

Deissler¹,

Lang²,

Lang³

2017

Cell Physiol Biochem

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Background/Aims: Hallmark of diabetic macular edema is the enhanced permeability of retinal endothelial cells (REC) induced by vascular endothelial growth factor (VEGF-A₁₆₅), which acts through activating specific receptors. To improve the predictability of inhibitors' potentials to block harmful effects of VEGF-A₁₆₅, we investigated if its signaling pathways triggered in REC are redundant. Methods: Immortalized bovine REC monolayers were treated with inhibitors specific for various protein kinases in combination with VEGF-A₁₆₅. Permeability was monitored continuously by measurements of the cell index (CI) to reveal even subtle and transient changes. Expression of tight junction (TJ) proteins was determined as additional indicator of barrier stability. Results: After a sharp but transient CI drop caused by VEGF-A₁₆₅ early after its addition, further exposure resulted in a continuous CI decline over several days associated with loss of TJ protein claudin-1. Both phases were blocked by inhibition of VEGF receptor 2. Tested inhibitors of intracellular kinases had a limited or no effect, or were efficient only in certain phases of exposure to VEGF-A₁₆₅, e.g. inhibiting protein kinase C only prevented the early response. High concentrations of some inhibitors even resulted in VEGF-independent barrier destabilization. Conclusions: Specific kinase inhibitors differently affect VEGF-A₁₆₅-triggered processes in distinct phases of its action. VEGF-A₁₆₅-initiated signaling is redundant and blocking of key proteins of single pathways is not sufficient to suppress REC barrier breakdown.

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Section: Discussionmentioning

confidence: 99%

Inhibition of Single Routes of Intracellular Signaling is Not Sufficient to Neutralize the Biphasic Disturbance of a Retinal Endothelial Cell Barrier Induced by VEGF-A165

Deissler¹,

Lang²,

Lang³

2017

Cell Physiol Biochem

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“…14). These structural distinctions between retinal and choroidal endothelial cells are born out by mRNA expression studies (Browning et al, 2012), proteomics (Zamora et al, 2007) and functional experiments as well (Stewart et al, 2011). …”

Section: Choriocapillaris Phenotype Change In Aging and Amdmentioning

confidence: 99%

Complement activation and choriocapillaris loss in early AMD: Implications for pathophysiology and therapy

Whitmore

Sohn

Chirco

et al. 2015

Progress in Retinal and Eye Research

189

160

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Age-related macular degeneration (AMD) is a common and devastating disease that can result in severe visual dysfunction. Over the last decade, great progress has been made in identifying genetic variants that contribute to AMD, many of which lie in genes involved in the complement cascade. In this review we discuss the significance of complement activation in AMD, particularly with respect to the formation of the membrane attack complex in the aging choriocapillaris. We review the clinical, histological and biochemical data that indicate that vascular loss in the choroid occurs very early in the pathogenesis of AMD, and discuss the potential impact of vascular dropout on the retinal pigment epithelium, Bruch's membrane and the photoreceptor cells. Finally, we present a hypothesis for the pathogenesis of early AMD and consider the implications of this model on the development of new therapies.

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“…Human umbilical vein endothelial cells (HUVECs) and human retinal microvascular endothelial cells (HRMECs) differ in a number of properties as well as in their gene expression profiles [31]. While the role of KLF family members, including KLF4, in HUVECs has been investigated, their role in HRMECs has not been investigated.…”

Section: Introductionmentioning

confidence: 99%

KLF4 Promotes Angiogenesis by Activating VEGF Signaling in Human Retinal Microvascular Endothelial Cells

Wang

Yang

et al. 2015

PLoS ONE

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The transcription factor Krüppel-like factor 4 (KLF4) has been implicated in regulating cell proliferation, migration and differentiation in a variety of human cells and is one of four factors required for the induction of pluripotent stem cell reprogramming. However, its role has not been addressed in ocular neovascular diseases. This study investigated the role of KLF4 in angiogenesis and underlying molecular mechanisms in human retinal microvascular endothelial cells (HRMECs). The functional role of KLF4 in HRMECs was determined following lentiviral vector mediated inducible expression and shRNA knockdown of KLF4. Inducible expression of KLF4 promotes cell proliferation, migration and tube formation. In contrast, silencing KLF4 inhibits cell proliferation, migration, tube formation and induces apoptosis in HRMECs. KLF4 promotes angiogenesis by transcriptionally activating VEGF expression, thus activating the VEGF signaling pathway in HRMECs.

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Comparative gene expression profiling of human umbilical vein endothelial cells and ocular vascular endothelial cells

Cited by 39 publications

References 24 publications

Inhibition of Single Routes of Intracellular Signaling is Not Sufficient to Neutralize the Biphasic Disturbance of a Retinal Endothelial Cell Barrier Induced by VEGF-A165

Inhibition of Single Routes of Intracellular Signaling is Not Sufficient to Neutralize the Biphasic Disturbance of a Retinal Endothelial Cell Barrier Induced by VEGF-A165

Complement activation and choriocapillaris loss in early AMD: Implications for pathophysiology and therapy

KLF4 Promotes Angiogenesis by Activating VEGF Signaling in Human Retinal Microvascular Endothelial Cells

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