BILATERAL DIFFUSE UVEAL MELANOCYTIC PROLIFERATION MISTAKEN FOR NIVOLUMAB-INDUCED VOGT-KOYANAGI-HARADA DISEASE-LIKE SYNDROME.

Background/purpose: To describe a case of bilateral diffuse uveal melanocytic proliferation (BDUMP) that was mistaken for nivolumab-induced Vogt-Koyanagi-Harada disease-like syndrome.

Methods: We present the case of a 58-year-old white man with metastatic renal clear cell carcinoma for which he was palliatively treated with IV nivolumab immunotherapy. The patient developed subacute onset of blurry vision and gray spots in the visual fields of both eyes, macular subretinal fluid, thickening of the retinal pigment epithelium, and swollen optic nerve heads.

The Role of Heparan Sulfate and Neuropilin 2 in VEGFA Signaling in Human Endothelial Tip Cells and Non-Tip Cells during Angiogenesis In Vitro.

During angiogenesis, vascular endothelial growth factor A (VEGFA) regulates endothelial cell (EC) survival, tip cell formation, and stalk cell proliferation via VEGF receptor 2 (VEGFR2). VEGFR2 can interact with VEGFR2 co-receptors such as heparan sulfate proteoglycans (HSPGs) and neuropilin 2 (NRP2), but the exact roles of these co-receptors, or of sulfatase 2 (SULF2), an enzyme that removes sulfate groups from HSPGs and inhibits HSPG-mediated uptake of very low density lipoprotein (VLDL), in angiogenesis and tip cell biology are unknown. In the present study, we investigated whether the modulation of binding of VEGFA to VEGFR2 by knockdown of or affects sprouting angiogenesis, tip cell formation, proliferation of non-tip cells, and EC survival, or uptake of VLDL.

IGF-binding proteins 3 and 4 are regulators of sprouting angiogenesis.

Purpose: We have previously identified insulin-like growth factor 2 (IGF2) and insulin-like growth factor 1 receptor (IGF1R) as essential proteins for tip cell maintenance and sprouting angiogenesis. In this study, we aim to identify other IGF family members involved in endothelial sprouting angiogenesis.

Methods: Effects on sprouting were analyzed in human umbilical vein endothelial cells (HUVECs) using the spheroid-based sprouting model, and were quantified as mean number of sprouts per spheroid and average sprout length.

Anti-angiogenic effects of crenolanib are mediated by mitotic modulation independently of PDGFR expression.

Background: Crenolanib is a tyrosine kinase inhibitor targeting PDGFR-α, PDGFR-β and Fms related tyrosine kinase-3 (FLT3) that is currently evaluated in several clinical trials. Although platelet-derived growth factor receptor (PDGFR) signalling pathway is believed to play an important role in angiogenesis and maintenance of functional vasculature, we here demonstrate a direct angiostatic activity of crenolanib independently of PDGFR signalling.

Methods: The activity of crenolanib on cell viability, migration, sprouting, apoptosis and mitosis was assessed in endothelial cells, tumour cells and fibroblasts.

IGF2 and IGF1R identified as novel tip cell genes in primary microvascular endothelial cell monolayers.

Tip cells, the leading cells of angiogenic sprouts, were identified in cultures of human umbilical vein endothelial cells (HUVECs) by using CD34 as a marker. Here, we show that tip cells are also present in primary human microvascular endothelial cells (hMVECs), a more relevant endothelial cell type for angiogenesis. By means of flow cytometry, immunocytochemistry, and qPCR, it is shown that endothelial cell cultures contain a dynamic population of CD34 cells with many hallmarks of tip cells, including filopodia-like extensions, elevated mRNA levels of known tip cell genes, and responsiveness to stimulation with VEGF and inhibition by DLL4.

Correction: CD34 Promotes Pathological Epi-Retinal Neovascularization in a Mouse Model of Oxygen-Induced Retinopathy.

[This corrects the article DOI: 10.1371/journal.pone.

Computational Screening of Tip and Stalk Cell Behavior Proposes a Role for Apelin Signaling in Sprout Progression.

Angiogenesis involves the formation of new blood vessels by sprouting or splitting of existing blood vessels. During sprouting, a highly motile type of endothelial cell, called the tip cell, migrates from the blood vessels followed by stalk cells, an endothelial cell type that forms the body of the sprout. To get more insight into how tip cells contribute to angiogenesis, we extended an existing computational model of vascular network formation based on the cellular Potts model with tip and stalk differentiation, without making a priori assumptions about the differences between tip cells and stalk cells.

CD34 Promotes Pathological Epi-Retinal Neovascularization in a Mouse Model of Oxygen-Induced Retinopathy.

The sialomucins CD34 and podocalyxin (PODXL) are anti-adhesive molecules expressed at the luminal membrane of endothelial cells of small blood vessels and facilitate vascular lumen formation in the developing mouse aorta. CD34 transcript and protein levels are increased during human angiogenesis, its expression is particularly enriched on endothelial tip cell filopodia and CD34 is a marker for tip cells in vitro. Here, we investigated whether CD34 merely marks endothelial tip cells or has a functional role in tip cells and angiogenesis.

Role of sulfatase 2 in lipoprotein metabolism and angiogenesis.

Purpose Of Review: This article summarizes the current evidence to support a role of sulfatase 2 (SULF2) in triglyceride-rich lipoprotein (TRL) metabolism and angiogenesis.

Recent Findings: Heparan sulfate proteoglycans (HSPG) are involved in the hepatic clearance of TRLs in mice and in humans. Different genetically modified mouse models have been instrumental to provide evidence that syndecan1, the core protein of HSPG, but also the degree of sulfation of the heparin sulfate chain, attached to syndecan 1, is important for hepatic TRL metabolism.