#vegf

Stopping Sprouts

Like roads in a city, veins in your body need careful mapping. When they don’t stick to the plan, sporadic vascular malformation – malformed veins – occur, causing pain and disfigurement. These veins form lesions containing genetically faulty cells (mutants). Currently, lesions often recur after treatment. Researchers now search for new therapeutics by growing mutant endothelial cells (ECs), collected from the veins of patients, in dishes. RNA sequencing revealed mutant ECs produced the signalling molecule TGFa. Fluorescence microscopy revealed when supporting cells from lesions (stromal cells) were grown alongside normal ECs, they triggered more EC sprouting (pictured, middle, right) compared with non-lesion stromal cells (left). Next, by grafting mutant ECs into mice, they found EC-produced TGFa triggered stromal cells to release the signalling molecule VEGFA. This caused EC sprouting and malformed veins. Treating mice with afatinib, a drug that interferes with VEGF signalling, decreased lesions, suggesting it may be a useful therapeutic.

Written by Lux Fatimathas

Image from work by Suvi Jauhiainen and Henna Ilmonen, and colleagues

A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland

Image originally published with a Creative Commons Attribution 4.0 International (CC BY 4.0)

Published in eLife, May 2023

Brain Leaks

Every heartbeat sends around a quarter of your blood volume to your brain, mainly via the blood-brain barrier – a network of blood vessels that don’t allow large molecules to leak out. However, certain parts of your brain have leakier blood vessels called fenestrated capillaries that do allow large molecules through. Researchers investigate how these vessels form using fluorescence microscopy of zebrafish brains with fluorescently-tagged blood vessels (pictured). They focused on signalling pathways already implicated in blood vessel development, Wnt and VEGF. Zebrafish lacking certain Wnt signalling molecules (bottom, top right) had severely disrupted blood-brain barrier vessels compared with normal brains (top left) while fenestrated capillaries were unaffected. Conversely, in zebrafish lacking different combinations of VEGF members, fenestrated blood vessels were severely disrupted. Notably, VEGFC and/or VEGFD were vital for fenestration and in certain regions, fenestration involved VEGFC interacting with VEGFA. A VEGF cocktail is, therefore, essential for developing fenestrated capillaries.

Written by Lux Fatimathas

Image from work by Sweta Parab and colleagues

Department of Neurosciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA

Image originally published with a Creative Commons Attribution 4.0 International (CC BY 4.0)

Published in eLife, May 2023

Leak Less

It’s no good repairing a broken plumbing system with new pipes that leak themselves. Something like this happens when researchers investigating the mechanism behind struggling lymphatic systems – the network of microscopic pipes that drain and transport essential material in the body – add the growth-inducing molecule VEGF-C to prompt new vessel growth. As an alternative to this active encouragement, a new approach instead removed the innate brakes downstream in the regulation process. The study examined mice engineered to lack a particular protein, PTEN, in the cells lining their vessels, which freed a different key receptor for VEGF-C to step up its action. The result was an expanded network of lymphatic vessels that was less leaky and functioned better. The vessels (green in the mouse intestinal tissue shown) were long-lasting, suggesting this approach may be a better way to enhance the network.

Written by Anthony Lewis

Image from work by Raghu P. Kataru and colleagues, on the cover of Science Signaling, 10 August 2021

Department of Surgery, Division of Plastic and Reconstructive Surgery, Memorial Sloan Kettering Cancer Center (MSKCC), New York, NY, USA

Image copyright held by and reproduced with permission from the AAAS

Published in Science Signaling, August 2021

Airways in Action

The air we breathe doesn't just contain gases but also dirt, debris and microbes. Thankfully the cells that line our airways have projections called cilia, which filter out these particles. In airway diseases, this process can be disturbed, which is why tissues with cilia are useful in lab studies of these diseases. However, it’s a challenge to maintain cilia in a dish. Here, researchers tested four different solutions in which cells can be grown to find out which is best at maintaining cilia. Cells were imaged using scanning electron microscopy (pictured), revealing that only one solution effectively maintained cilia (left) while the others didn't (examples middle and right). The winning solution succeeded because of the balance of high enough levels of the chemical retinoic acid and low levels of the chemicals VEGF, EGF and FGF-β. These results will help future researchers better study airway tissue and diseases in the lab.

Written by Lux Fatimathas

Image adapted from work by Anja E. Luengen and colleagues

Department of Biohybrid and Medical Textiles (BioTex), AME - Institute of Applied Medical Engineering, Helmholtz Institute, RWTH Aachen University, Aachen, Germany

Image originally published under a Creative Commons Licence (BY 4.0)

Published in Scientific Reports, April 2020

Launching Vessels

Bartonella henselae (B. henselae) are bacteria carried in insect bites that use a sneaky trick to avoid detection. They somehow urge their hosts to produce new vascular endothelial cells, prompting the creation of new blood vessels, or angiogenesis – confusing the immune system but attracting the attention of scientists. Researchers found that B. henselae make a protein, now known as BafA that acts like a vascular endothelial growth factor, which commonly coax vessel development in mammals like humans. In fact in these samples of a mouse’s aorta (artificially coloured green), exposure to BafA causes new vessels to sprout (right) compared to the vessel chunk without BafA (left). Researchers now have lots of options – using BafA to grow vessels for study in the lab perhaps, or one day turning these plucky invaders – that can cause Cat-scratch disease – into medical helpers used in regenerative medicine to restore damaged circulation.

Written by John Ankers

Image from work by Kentaro Tsukamoto and colleagues

Department of Microbiology, Fujita Health University School of Medicine, Toyoake, Aichi, Japan

Image originally published with a Creative Commons Attribution 4.0 International (CC BY 4.0)

Published in Nature Communications, July 2020

Blood Shot

Like all of our healthy tissues, our eyes are riddled with blood vessels – vascular networks which supply valuable chemicals to our peepers. But a condition called iris neovascularisation (INV) can cause vessel overgrowth, leading to rubeosis iridis and a type of glaucoma. Here two techniques investigate a promising treatment for INV in the eye of a 79-year old man – injections which aim to control a protein called VEGF inside eye cells, taming blood vessel growth. On the top, patterns of blood flow around the iris (seen in red on the cross-section on the right) are used to map out the blood vessel network using a computer algorithm (left). Underneath, the VEGF treatment (bottom) has clearly reduced the INV. Further developments may make these techniques more sensitive, allowing ophthalmologists to detect and treat eye problems earlier in life.

Written by John Ankers

Image adapted from work by Daiki Shiozaki and colleagues

Department of Ophthalmology, Osaka University Graduate School of Medicine, Suita, Japan

Image originally published under a Creative Commons Licence (BY 4.0)

Published in Scientific Reports, July 2019