scholarly journals Largazole Inhibits Ocular Angiogenesis by Modulating the Expression of VEGFR2 and p21

Marine Drugs ◽  
2021 ◽  
Vol 19 (8) ◽  
pp. 471
Author(s):  
Beiying Qiu ◽  
Alison Tan ◽  
Yu Zhi Tan ◽  
Qi-Yin Chen ◽  
Hendrik Luesch ◽  
...  
Keyword(s):  
Vascular Endothelial Cells ◽  
Vascular Endothelial Cell ◽  
Vascular Endothelial ◽  
Ocular Angiogenesis ◽  
Anti Vegf ◽  
Metatarsal Bones ◽  
Number Of Patients ◽  
Choroidal Vasculature ◽  
Characteristic Features

Ocular angiogenic diseases, characterized by abnormal blood vessel formation in the eye, are the leading cause of blindness. Although Anti-VEGF therapy is the first-line treatment in the market, a substantial number of patients are refractory to it or may develop resistance over time. As uncontrolled proliferation of vascular endothelial cells is one of the characteristic features of pathological neovascularization, we aimed to investigate the role of the class I histone deacetylase (HDAC) inhibitor Largazole, a cyclodepsipeptide from a marine cyanobacterium, in ocular angiogenesis. Our study showed that Largazole strongly inhibits retinal vascular endothelial cell viability, proliferation, and the ability to form tube-like structures. Largazole strongly inhibits the vessel outgrowth from choroidal explants in choroid sprouting assay while it does not affect the quiescent choroidal vasculature. Largazole also inhibits vessel outgrowth from metatarsal bones in metatarsal sprouting assay without affecting pericytes coverage. We further demonstrated a cooperative effect between Largazole and an approved anti-VEGF drug, Alflibercept. Mechanistically, Largazole strongly inhibits the expression of VEGFR2 and leads to an increased expression of cell cycle inhibitor, p21. Taken together, our study provides compelling evidence on the anti-angiogenic role of Largazole that exerts its function through mediating different signaling pathways.

Alterations in Vascular Endothelial Cell-related Plasma Proteins In Thalassaemic Patients and their Correlation with Clinical Symptoms

1995 ◽  
Vol 74 (04) ◽  
pp. 1045-1049 ◽  
Author(s):  
P Butthep ◽  
A Bunyaratvej ◽  
Y Funahara ◽  
H Kitaguchi ◽  
S Fucharoen ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Immunosorbent Assay ◽  
Plasma Proteins ◽  
Clinical Symptoms ◽  
Vascular Endothelial Cells ◽  
Vascular Endothelial Cell ◽  
Enzyme Linked Immunosorbent Assay ◽  
Vascular Endothelial ◽  
Leg Ulcers

SummaryAn increased level of plasma thrombomodulin (TM) in α- and β- thalassaemia was demonstrated using an enzyme-linked immunosorbent assay (ELISA). Nonsplenectomized patients with β-thalassaemia/ haemoglobin E (BE) had higher levels of TM than splenectomized cases (BE-S). Patients with leg ulcers (BE-LU) were found to have the highest increase in TM level. Appearance of larger platelets in all types of thalassaemic blood was observed indicating an increase in the number of younger platelets. These data indicate that injury of vascular endothelial cells is present in thalassaemic patients.

Effect of Neuroinflammation on ABC Transporters: Possible Contribution to Refractory Epilepsy

2018 ◽  
Vol 17 (10) ◽  
pp. 728-735 ◽  
Author(s):  
Xiaolin Deng ◽  
Yangmei Xie ◽  
Yinghui Chen
Keyword(s):  
Antiepileptic Drugs ◽  
Abc Transporters ◽  
Refractory Epilepsy ◽  
Vascular Endothelial Cells ◽  
Efflux Transporters ◽  
Vascular Endothelial ◽  
Intracellular Signalling Pathways ◽  
The Brain ◽  
Transporter Expression

Background & Objective: Epilepsy is a common and serious chronic neurological disorder that is mainly treated with antiepileptic drugs. Although current antiepileptic drugs used in clinical practice have advanced to the third generation, approximately one-third of patients are refractory to these treatments. More efficacious treatments for refractory epilepsy are therefore needed. A better understanding of the mechanism underlying refractory epilepsy is likely to facilitate the development of a more effective therapy. The abnormal expression and/or dysfunction of efflux transporters, particularly ABC transporters, might contribute to certain cases of refractory epilepsy. Inflammation in the brain has recently been shown to regulate the expression and/or function of ABC transporters in the cerebral vascular endothelial cells and glia of the blood-brain barrier by activating intracellular signalling pathways. Conclusion: Therefore, in this review, we will briefly summarize recent research advances regarding the possible role of neuroinflammation in regulating ABC transporter expression in epilepsy.

scholarly journals Emerging Role of AP-1 Transcription Factor JunB in Angiogenesis and Vascular Development

2021 ◽  
Vol 22 (6) ◽  
pp. 2804
Author(s):  
Yasuo Yoshitomi ◽  
Takayuki Ikeda ◽  
Hidehito Saito-Takatsuji ◽  
Hideto Yonekura
Keyword(s):  
Endothelial Cells ◽  
Transcription Factor ◽  
Blood Vessel ◽  
Vascular Endothelial Cells ◽  
Vascular Development ◽  
Endothelial Cell Migration ◽  
Vascular Endothelial ◽  
Blood Vessel Formation ◽  
Vessel Formation

Blood vessels are essential for the formation and maintenance of almost all functional tissues. They play fundamental roles in the supply of oxygen and nutrition, as well as development and morphogenesis. Vascular endothelial cells are the main factor in blood vessel formation. Recently, research findings showed heterogeneity in vascular endothelial cells in different tissue/organs. Endothelial cells alter their gene expressions depending on their cell fate or angiogenic states of vascular development in normal and pathological processes. Studies on gene regulation in endothelial cells demonstrated that the activator protein 1 (AP-1) transcription factors are implicated in angiogenesis and vascular development. In particular, it has been revealed that JunB (a member of the AP-1 transcription factor family) is transiently induced in endothelial cells at the angiogenic frontier and controls them on tip cells specification during vascular development. Moreover, JunB plays a role in tissue-specific vascular maturation processes during neurovascular interaction in mouse embryonic skin and retina vasculatures. Thus, JunB appears to be a new angiogenic factor that induces endothelial cell migration and sprouting particularly in neurovascular interaction during vascular development. In this review, we discuss the recently identified role of JunB in endothelial cells and blood vessel formation.

scholarly journals Role of the retinal vascular endothelial cell in ocular disease

2013 ◽  
Vol 32 ◽  
pp. 102-180 ◽  
Author(s):  
Arpita S. Bharadwaj ◽  
Binoy Appukuttan ◽  
Phillip A. Wilmarth ◽  
Yuzhen Pan ◽  
Andrew J. Stempel ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Vascular Endothelial Cell ◽  
Ocular Disease ◽  
Vascular Endothelial ◽  
Retinal Vascular Endothelial Cell

Enhanced Vascular Endothelial Cell Function on Nanostructured Titanium Surface Features: The Role of Nano to Submicron Roughness

2008 ◽  
Vol 1136 ◽  
Author(s):  
Jing Lu ◽  
Dongwoo Khang ◽  
Thomas J. Webster
Keyword(s):  
Cell Adhesion ◽  
Endothelial Cell ◽  
Cell Function ◽  
Vascular Endothelial Cell ◽  
Vascular Endothelial ◽  
Endothelial Cell Function ◽  
Titanium Surfaces ◽  
Endothelial Cell Adhesion

ABSTRACTTo study the contribution of different surface feature properties in improving vascular endothelial cell adhesion, rationally designed nano/sub-micron patterns with various dimensions were created on titanium surfaces in this study. In vitro results indicated that endothelial cell adhesion was improved when the titanium pattern dimensions decreased into the nano-scale. Specifically, endothelial cells preferred to adhere on sub-micron and nano rough titanium substrates compared to flat titanium. Moreover, titanium with nano and sub-micron roughness and with the same chemistry as compared to flat titanium, had significantly greater surface energy. Thus, the present study indicated the strong potential of surface nanotopography and nano/sub-micron roughness for improving current vascular stent design.

scholarly journals Endothelial Microsomal Prostaglandin E Synthetase-1 Upregulates Vascularity and Endothelial Interleukin-1β in Deteriorative Progression of Experimental Autoimmune Encephalomyelitis

2018 ◽  
Vol 19 (11) ◽  
pp. 3647 ◽  
Author(s):  
Takako Takemiya ◽  
Marumi Kawakami ◽  
Chisen Takeuchi
Keyword(s):  
Experimental Autoimmune Encephalomyelitis ◽  
Vascular Endothelial Cells ◽  
Immunohistochemical Analysis ◽  
Interleukin 1Β ◽  
Prostaglandin E ◽  
Vascular Endothelial ◽  
Autoimmune Encephalomyelitis ◽  
Ep Receptor ◽  
Experimental Autoimmune

Microsomal prostaglandin E synthetase-1 (mPGES-1) is an inducible terminal enzyme for the production of prostaglandin E2 (PGE2). In experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis, mPGES-1 is induced in vascular endothelial cells (VECs) around inflammatory foci and facilitates inflammation, demyelination, and paralysis. Therefore, we investigated the role of CD31-positive VECs in mPGES-1-mediated EAE aggravation using immunohistochemical analysis and imaging of wild-type (wt) and mPGES-1-deficient (mPGES-1−/−) mice. We demonstrated that EAE induction facilitated vascularity in inflammatory lesions in the spinal cord, and this was significantly higher in wt mice than in mPGES-1−/− mice. In addition, endothelial interleukin-1β (IL-1β) production was significantly higher in wt mice than in mPGES-1−/− mice. Moreover, endothelial PGE2 receptors (E-prostanoid (EP) receptors EP1–4) were expressed after EAE induction, and IL-1β was induced in EP receptor-positive VECs. Furthermore, IL-1 receptor 1 expression on VECs was increased upon EAE induction. Thus, increased vascularity is one mechanism involved in EAE aggravation induced by mPGES-1. Furthermore, mPGES-1 facilitated the autocrine function of VECs upon EP receptor induction and IL-1β production, modulating mPGES-1 induction in EAE.

scholarly journals Emerging Role of Immune Therapy in HCC

2021 ◽  
Author(s):  
Stacey M. Stein
Keyword(s):  
Kinase Inhibitors ◽  
Immune Therapy ◽  
Treatment Options ◽  
Single Agent ◽  
Small Subset ◽  
Vascular Endothelial ◽  
Number Of Patients ◽  
Endothelial Growth Factor ◽  
Expected Increase

AbstractHepatocellular carcinoma (HCC) remains a prevalent cancer diagnosis with an expected increase in incidence in the next decade. Treatment options for advanced disease have expanded significantly in the last decade since sorafenib was first approved in 2007. There have been approvals for multiple tyrosine kinase inhibitors (TKIs) with modest improvements in survival. Single-agent PD-1 inhibition has shown responses in ∼15% of patients, with a tail of the curve that is very beneficial to a small subset of patients. Most recently, studies of combination therapy with immune therapy drugs are showing more durable responses in a larger number of patients with unprecedented response rates over 30%. Different strategies have been pursued, including PD-1 and PD-L1 combinations with vascular endothelial growth factor inhibition, TKIs, and anti-CTLA-4 antibodies. This article provides a review of studies both completed and ongoing with immune therapy in advanced HCC.

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