Negative regulators of angiogenesis, ocular vascular homeostasis, and pathogenesis and treatment of exudative AMD

Farnoodian, Mitra; Sorenson, Christine M.

doi:10.4103/jovr.jovr_67_18

Cited by 22 publications

(14 citation statements)

References 160 publications

(208 reference statements)

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“…It is well known that genomic methylation and dimethyl transferase activity are increased in tumour endothelial cells leading to angiogenesis and cell growth. This may mediated by inactivation of angiogenesis inhibitory genes such as; thrombospondin-1 (TSP1) and insulin-like growth factor binding protein-3 (IGFBP3) genes [43,45,46]. These observations are in agreement with previous studies, which reported that Methyltransferase inhibitors (5-AazD or zebularine) decreased vessel formation and inhibited angiogenesis in different tumour models [47].…”

Section: Discussionsupporting

confidence: 88%

5-aza-2’-deoxycytidine induces apoptosis and inhibits tumour growth in vivo of FaDu cells, a specific HPVnegative HNSCC cell line

et al. 2021

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Head and neck cancer squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide, resulting in over 600,000 new diagnoses annually. Traditionally, HNCC has been related to tobacco and alcohol exposure; however, over the past decade, a growing number of head and neck cancers are attributed to human papillomavirus (HPV) infection. 5-Aza-2’-deoxycytidine (5-AzaD) was demonstrated as an effective chemotherapeutic agent for acute myelogenous leukaemia. Preclinical data revealed that 5-aza inhibits growth and increases cell death of HPV(+) cancer cells. These effects are associated with reduced expression of HPV genes, stabilization of TP53, and activation of TP53-dependent apoptosis. The aim of the present study is to test the effect of 5-AzaD on growth of human squamous cell carcinoma (FaDu), a HPV(-) and p53 mutated cells, in vitro and in vivo. The effect of 5-AzaD on cell viability, cell cycle progression and induction of apoptosis was tested in vitro. The effect of 5-AzaD on tumour growth in vivo was tested using xenograft mice inoculated with FaDu cells. The results indicated that 5-AzaD reduced cell viability and induced apoptosis in FaDu cells in vitro. In vivo studies revealed that 5-AzaD suppresses the growth of tumours in xenograft mice inoculated with FaDu cells through inhibition of proliferation and induction of apoptosis. These findings may emphasis that 5-AzaD is effective in treatment of HPV(-) HNSCC tumours through TP53 independent pathway. Future studies are needed in order to clarify the molecular mechanism of action of 5-AzaD in HPV(-) cancer cells.

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Section: Discussionsupporting

confidence: 88%

5-aza-2’-deoxycytidine induces apoptosis and inhibits tumour growth in vivo of FaDu cells, a specific HPVnegative HNSCC cell line

et al. 2021

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“…Angiogenesis has a central role in the metabolism not only of normal tissue (during embryonic and fetal development, or wound healing processes), but also of tissues under pathological conditions, as in diabetic retinopathy, age-related macular degeneration, retinopathy of prematurity, or tumors [ 40 , 41 ]. It is relevant that hemodynamic forces are directly related to the regulation of angiogenesis [ 40 , 42 ].…”

Section: Discussionmentioning

confidence: 99%

“…It is relevant that hemodynamic forces are directly related to the regulation of angiogenesis [ 40 , 42 ]. Studies have demonstrated direct modulatory mechanical force effects of SS and cell stretch on adhesion, migration and morphogenesis of ECs [ 16 , 41 , 43 ]. Lesions in the vascular endothelium are common several processes such as inflammation and atherosclerosis where SS usually is low and/or is turbulent.…”

Section: Discussionmentioning

confidence: 99%

Altered shear stress on endothelial cells leads to remodeling of extracellular matrix and induction of angiogenesis

et al. 2020

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Endothelial cells (ECs) are subjected to physical forces such as shear stress (SS) induced by blood flow that leads to significant changes in morphology, physiology and gene expression. The abnormal mechanical forces applied in the cardiovascular system can influence the development of conditions and diseases such as thrombosis, hypertension and atherosclerosis. This study investigated the expression of glycosaminoglycans (GAGs), proteoglycans and extracellular matrix molecules in ECs exposed to normal and altered SS. ECs were exposed to SS of 12 dyn/cm2 (artery physiological condition) and 4 dyn/cm2 (artery pathological condition). Subsequently, ECs were subjected to immunofluorescence, qPCR, GAG biosynthesis analyses and cell-based assays. SS induced changes in ECs morphology. There were other pathological consequences of altered SS, including inhibited adhesion, stimulation of migration and capillary-like tube formation, as well as increases of GAG synthesis. We observed higher expression of syndecan-4, perlecan, decorin, fibronectin and collagen III α1 and growth factors, including VEGF-A and TGFβ-1. ECs exposed to SS displayed extracellular matrix remodeling as well as expression of cell-matrix and cell-cell interaction molecules. This study contributes to the understanding of how vascular biology is affected by mechanical forces and how these molecules can be affected in cardiovascular diseases.

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“…The stages of AMD include hard drusen, which is associated with localized malfunctions of the retinal pigment epithelium, soft drusen associated with diffuse dysfunction of the retinal pigment epithelium, and damage to photoreceptors [ 4 ]. In retinal degeneration, pigment epithelium-derived factor (PEDF), which is produced in retinal pigment epithelial (RPE) cells and maintains retinal homeostasis, is decreased, while the expression of vascular endothelial growth factor (VEGF) is increased [ 5 , 6 ].…”

Section: Introductionmentioning

confidence: 99%

PEDF-Mediated Mitophagy Triggers the Visual Cycle by Enhancing Mitochondrial Functions in a H2O2-Injured Rat Model

Kim

Park

et al. 2021

Cells

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Retinal degenerative diseases result from oxidative stress and mitochondrial dysfunction, leading to the loss of visual acuity. Damaged retinal pigment epithelial (RPE) and photoreceptor cells undergo mitophagy. Pigment epithelium-derived factor (PEDF) protects from oxidative stress in RPE and improves mitochondrial functions. Overexpression of PEDF in placenta-derived mesenchymal stem cells (PD-MSCs; PD-MSCsPEDF) provides therapeutic effects in retinal degenerative diseases. Here, we investigated whether PD-MSCsPEDF restored the visual cycle through a mitophagic mechanism in RPE cells in hydrogen peroxide (H2O2)-injured rat retinas. Compared with naïve PD-MSCs, PD-MSCsPEDF augmented mitochondrial biogenesis and translation markers as well as mitochondrial respiratory states. In the H2O2-injured rat model, intravitreal administration of PD-MSCsPEDF restored total retinal layer thickness compared to that of naïve PD-MSCs. In particular, PTEN-induced kinase 1 (PINK1), which is the major mitophagy marker, exhibited increased expression in retinal layers and RPE cells after PD-MSCPEDF transplantation. Similarly, expression of the visual cycle enzyme retinol dehydrogenase 11 (RDH11) showed the same patterns as PINK1 levels, resulting in improved visual activity. Taken together, these findings suggest that PD-MSCsPEDF facilitate mitophagy and restore the loss of visual cycles in H2O2-injured rat retinas and RPE cells. These data indicate a new strategy for next-generation MSC-based treatment of retinal degenerative diseases.

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Negative regulators of angiogenesis, ocular vascular homeostasis, and pathogenesis and treatment of exudative AMD

Cited by 22 publications

References 160 publications

5-aza-2’-deoxycytidine induces apoptosis and inhibits tumour growth in vivo of FaDu cells, a specific HPVnegative HNSCC cell line

5-aza-2’-deoxycytidine induces apoptosis and inhibits tumour growth in vivo of FaDu cells, a specific HPVnegative HNSCC cell line

Altered shear stress on endothelial cells leads to remodeling of extracellular matrix and induction of angiogenesis

PEDF-Mediated Mitophagy Triggers the Visual Cycle by Enhancing Mitochondrial Functions in a H2O2-Injured Rat Model

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