|| February 17: 2019: University of Exeter News || ά. Scientists have discovered new ways, in which, the body regulates blood clots, in a discovery, which could, one day, lead to the development of better treatments, that could help prevent and treat conditions, including, heart diseases, Stroke and Vascular Dementia. Led by the University of Exeter academics and funded by the British Heart Foundation, the researchers have developed a new technique, that allows them to, simultaneously, measure blood clotting and the formation of free radicals.

Free radicals are unstable molecules, containing unpaired single electrons, seeking to pair up. This makes these molecules highly reactive, that are able to modify protein, lipids and DNA. Amongst other unwanted effects, free radicals play a role in the build-up of blood clots, which, in turn, are considered a key driver in the development of a range of conditions, including, heart diseases, Stroke, Dementia and inflammation-related conditions, such as, Arthritis. The new technique is outlined in research, published in Haematologica.

The technique combines electron para-magnetic resonance, an advanced method for detecting free radicals, with blood cell aggregometry, an established technique for measuring blood clotting. The research team has, successfully, used the technique in mice and in human cells. They aim to better understand how blood cells function, which will help in the development of new drugs against blood clotting diseases or to test the risk of clotting diseases in patients.

Dr Giordano Pula, of the University of Exeter Medical School, who led the Study, said, “We’re really excited to discover this new technique and its potential to understand how blood vessel diseases develop. For the first time, we can, now, simultaneously, measure blood clotting and the formation of free radicals. We know, they play a key role in blood vessel damage, caused by ageing, diabetes, obesity and chronic inflammation. We’re currently using this technique in our efforts to develop a new treatment to protect the blood vessels in diseases, such as, heart diseases, Stroke, Obesity and Vascular Dementia.”

The Researcher team, which includes other academics in the laboratory of Professor Patrick Pagano at the University of Pittsburgh, US, discovered that the enzymes NADPH oxidases are critically important for the generation of free radicals, the stimulation of blood clotting and the promotion of blood vessel damage in patients.

Professor Jeremy Pearson, the Associate Medical Director at the British Heart Foundation, said, “With BHF funding, Dr Pula has developed an improved method to investigate part of the blood clotting process, which focuses on the ways, in which platelets from blood samples clump together.

This method, may be, useful for future studies looking into new anti-platelet treatments for diseases, such as, Diabetes, where clotting is disturbed and increases the risk of Heart Attack or Stroke.”

The Paper: A novel combinatorial technique for simultaneous quantification of oxygen radicals and aggregation reveals unexpected redox patterns in the activation of platelets by different physiopathological stimuli https://doi.org/10.3324/haematol.2018.208819:::ω.

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In Vitro Grafts Increase Blood Flow in Infarcted Rat Hearts

|| February 06: 2019: University of Washington News || ά. Advances in stem cell research offer hope for treatments, that could help patients regrow heart muscle tissue after heart attacks, a key to achieving more complete recovery. Scientists report success in creating functional blood vessels in vitro for hearts of rats that had sustained a heart attack. The Paper has been published in The Journal Nature Communications. The scientists set out to show that by growing stem cell-derived heart tissue in a petri dish, with attention to blood vessels’ construction, they could improve the tissue’s incorporation with existing heart vessels.

The research team used human stem cells to create a vascularised construct or patch, with a functioning network of blood vessels, that mimics the vasculature of a human heart. “To our knowledge, this is the first demonstration that building organised blood vessels with perfusion outside the body leads to improved integration with host blood vessels and better tissue blood flow.” said Mr Zheng, a University of Washington Associate Professor of Bio-engineering. I come from a mechanical background. I love thinking about the dynamics of blood flow. Our whole bodies are vascularised. This network of vessels is dynamic and interconnected, like a transportation system, that remodels itself all the time.

Being able to organise the vessels in the tissue outside the body was very important. When we implanted the patch, we saw that the stem cell-derived tissue integrated effectively with the host’s coronary circulation. This improved blood flow to the engineered tissue and gave it the nutrients it needed to survive.”

‘’Disruption to blood flow during a heart attack leads to significant loss of heart muscle and heart function. Heart muscle, grown from stem cells, must, not only survive and integrate with the host tissue but, it, must, also, restore adequate blood flow.’’ said Professor Murry, of Pathology, Bio-engineering and Medicine:Cardiology atht University.

Optical micro-angiography imaging techniques, developed by Professor Ricky Wang, of the Bio-engineering, showed that blood flow within the grafts was twentyfold higher than has been reported for any other such graft. This suggested, according to researchers, that nurturing the tissue in the lab had a meaningful benefit for the heart cells before they were implanted into the rats’ hearts.

The research was funded by National Institutes of Health grant.

The Paper: Patterned human microvascular grafts enable rapid vascularization and increase perfusion in infarcted rat hearts: Meredith A Redd, Nicole Zeinstra, Wan Qin, Wei Wei, Amy Martinson, Yuliang Wang, Ruikang K Wang, Charles E Murry and Ying Zheng: Published in The Journal Nature Communications

Caption: Histology slides show murine heart at five days post-implant a: with conventional non-perfusable vessels and b: with patterned perfusable cardiac construct: Image: Nicole Zeinstra: University of Washington Bio-engineering:::ω.

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