Creepy_Toe2680 OP t1_j71p0lp wrote

Research has identified suPAR as a protein that contributes to the development of atherosclerosis and kidney disease, offering new opportunities for treatment.

Traditionally, clinicians have approached the treatment of cardiovascular disease by controlling diabetes and blood pressure, and utilizing medications such as aspirin and statins to lower cholesterol.

However, heart disease continues to be the leading cause of death in the United States. Even when risk factors are managed, many patients still experience heart attacks, according to Salim Hayek, M.D., physician-scientist and medical director of the University of Michigan Health Frankel Cardiovascular Clinics.

But a study led by Michigan Medicine has uncovered a protein produced by the immune system that causes atherosclerosis – the hardening of arteries that affects over a billion people worldwide – which offers the promise of new treatments.

“Targeting the immune component central to the development of atherosclerosis is the Holy Grail for the treatment of heart disease,” said Hayek, senior author of the study “This is the first time that a component of the immune system is identified that meets all the requirements for being a promising treatment target for atherosclerosis.”

This protein, called soluble urokinase plasminogen activator receptor, or suPAR, is produced by the bone marrow. It acts as a regulator, essentially a thermostat for the activity of the immune system, or “immunostat”.

Past studies have shown suPAR to be a marker of cardiovascular disease. But this study, published in the Journal of Clinical Investigation, is the first evidence showing that the protein actually causes atherosclerosis when at high levels.

Three-pronged findings

First, the research team analyzed the Multi-Ethnic Study of Atherosclerosis, which consists of over 5,000 people without known cardiovascular disease and found that those who had higher suPAR levels were much more prone to develop atherosclerosis and experience cardiovascular events, regardless of their underlying risk factors.

Then, the investigators did a genetic study of 24,000 people to find whether certain genetic variations affected levels of suPAR in blood. They discovered a specific variant in the gene PLAUR that codes for suPAR, and people with that genetic variant tended to have higher suPAR levels. Most importantly, that genetic variant was linked to atherosclerosis in a Mendelian randomization analysis of 500,000 participants in the UK Biobank, which was replicated in two other large data sets.

“We also found that participants lacking a copy of the PLAUR gene have a lower risk of heart disease,” said first author and geneticist George Hindy, M.D., Ph.D., of Regeneron Genetics Center. “Altogether, the genetic data is truly compelling for high suPAR being a cause of atherosclerosis.”

Finally, in mouse models with high suPAR levels, researchers saw a dramatic increase in atherosclerotic plaques of mouse aortas compared to mice with normal suPAR levels.

“Even prior to developing atherosclerosis, the mouse aortas with high suPAR levels contained more inflammatory white blood cells, and the immune cells circulating in the blood were in an activated state, or ‘attack-mode,’” said Daniel Tyrrell, Ph.D., co-first author and research fellow at the U-M Health Frankel Cardiovascular Center. “High suPAR levels appear to activate the immune cells and prime them to overreact to the high cholesterol environment, causing these cells to enter the blood vessel wall and accelerate the development of atherosclerosis.”

What is unique about this study, Hayek says, is that it brings to light high-quality clinical, genetic, and experimental data – all pointing to suPAR as a cause of atherosclerotic disease.

“Now, we’re looking into developing treatments to reduce suPAR levels safely as a strategy to prevent and treat heart disease, especially since traditional therapies for atherosclerosis have no impact on suPAR,” he said.

suPAR linking kidney and cardiovascular disease

The study dovetails findings that suPAR is known to be a pathogenic factor that causes kidney disease, which impacts one in seven Americans. People often experience the two conditions together: two-thirds of people with kidney disease are affected by cardiovascular disease, and over 40% of patients with cardiovascular disease have signs of kidney disease.

“This paper places suPAR as the link between kidney and cardiovascular disease; a common factor causing both through this inappropriate, persistent activation of the immune system,” said co-author Jochen Reiser, M.D., Ph.D., chair of the Department of Medicine at Rush University and an expert in the study of suPAR. “This is pointed out in the Mendelian randomization genetic analysis done by the investigators, showing that high suPAR is also linked to kidney disease.”

For both conditions, suPAR has long been known as a biomarker for poor outcomes and disease progression. In a 2020 study, Hayek’s team found that suPAR can worsen acute kidney injury and that blocking suPAR prevents it. A recent study led by Hayek found that levels of protein are high in patients with heart failure and predict death for patients.

Research into suPAR’s role in health and disease has advanced rapidly in the past 10 years. Hayek says suPAR has great potential to be a successful treatment target for cardiovascular and kidney disease. His lab has already begun work designing anti-suPAR therapies and planning clinical trials.

“My hope is that we are able to provide these treatments to our patients within the next three to five years,” he said. “This will be a game changer for the treatment of atherosclerotic and kidney disease”.

Reference: “Increased soluble urokinase plasminogen activator levels modulate monocyte function to promote atherosclerosis” by George Hindy, Daniel J. Tyrrell, Alexi Vasbinder, Changli Wei, Feriel Presswalla, Hui Wang, Pennelope Blakely, Ayse Bilge Ozel, Sarah Graham, Grace H. Holton, Joseph Dowsett, Akl C. Fahed, Kingsley-Michael Amadi, Grace K. Erne, Annika Tekmulla, Anis Ismail, Christopher Launius, Nona Sotoodehnia, James S. Pankow, Lise Wegner Thørner, Christian Erikstrup, Ole Birger Pedersen, Karina Banasik, Søren Brunak, Henrik Ullum, Jesper Eugen-Olsen, Sisse Rye Ostrowski, on behalf of the DBDS Consortium, Mary E. Haas, Jonas B. Nielsen, Luca A. Lotta, on behalf of the Regeneron Genetics Center, Gunnar Engström, Olle Melander, Marju Orho-Melander, Lili Zhao, Venkatesh L. Murthy, David J. Pinsky, Cristen J. Willer, Susan R. Heckbert, Jochen Reiser, Daniel R. Goldstein, Karl C. Desch and Salim S. Hayek, 4 October 2022, Journal of Clinical Investigation.

DOI: 10.1172/JCI158788

The study was funded by the National Heart, Lung, and Blood Institute (NHLBI), the Michigan Institute for Clinical & Health Research (MICHR), and the Gilead Sciences Research Scholar Program in Cardiovascular Disease.

Hayek and the University of Michigan have patents filed for the use of suPAR levels in the management of cardiovascular disease and the use anti-suPAR therapies as a strategy to prevent and treat atherosclerosis. Hayek and Reiser are scientific advisory board members of Walden Biosciences, a company devising therapeutics targeting suPAR in kidney disease. Hindy, Haas, Nielsen and Lotta receive salary, stocks and stock options from Regeneron Pharmaceuticals, Inc. Eugen-Olsen is a co-founder, shareholder, and chief scientific officer of Virogates and a named inventor on patents related to suPAR.


Creepy_Toe2680 OP t1_j6ieazl wrote

old article from 2022 oct I might add!

🕊- Supporting Iranians protesting for

women's rights

☢-Re-entering the

nuclear deal with Iran

💭Not sure






























Creepy_Toe2680 OP t1_j6how4h wrote

uhh looks like i have to do some research and math here soo..

The rocket engine, according to the plan, worked for 3.2 s, accelerating the rocket to a speed of about 90 m/s, which allowed the rocket to reach an altitude of 450 m.

The detonation shockwave travels significantly faster than the deflagration wave leveraged by today's jet engines, Trimble explained: up to 2,000 meters per second (4,475 miles per hour) compared to 10 meters per second from deflagration.

i am gonna use the second one (but i don't know if it is talking about the vehicle or the wave.)

distance from mars (130,000,000 km)

speed of detonating engine = 2km/s

so, 130000000/2= 65000000 seconds = 752.31481481 days or 2 years and 22 days.

not sure don't quote me on this.

edit: YES I knew it i was right that i was wrong!


Creepy_Toe2680 OP t1_j6hnffp wrote

Nuclear powered

>This isn’t the only way that NASA is looking at revolutionizing deep space travel. The space agency is reportedly looking into nuclear-powered spacecraft, which would allow spacecraft to travel further distances without needing liquid fuel. It would also make the journey to Mars significantly shorter, from six months to just 45 days.


Creepy_Toe2680 OP t1_j6hkn5m wrote

The new tech is called a rotating detonation rocket engine, or RDRE. This propulsion system uses detonations to generate thrust. To do this, the tech relies on the accelerating of a supersonic exothermic front, which similarly creates thrust to the way a shockwave travels through the atmosphere after an explosion, which could make deep space travel easier to build for.

The point of the design is to use less fuel while also providing more thrust than the current propulsion systems that NASA and other rocket-building companies rely on. Using less fuel makes it easier to prepare these spacecraft for deep space travel, as you can mete out smaller amounts of fuel that won’t weigh down the rocket when it is lifting off.

With the success of this test, NASA is now looking at building a working, fully reusable 10,00-pound RDRE that it can then compare to the performance of traditional liquid rocket engines – like those used in the Space Launch System. If those tests prove successful, too, and the comparisons play out well, it could revolutionize how we think about deep space travel in the future.

This isn’t the only way that NASA is looking at revolutionizing deep space travel. The space agency is reportedly looking into nuclear-powered spacecraft, which would allow spacecraft to travel further distances without needing liquid fuel. It would also make the journey to Mars significantly shorter, from six months to just 45 days.

by Joshua Hawkins (not me)


Creepy_Toe2680 OP t1_j5602ms wrote

State of lab grown eyes (not part of the article)

Regeneration of eyes as of 2019, June 25

There are still many challenges to address before we can use eyes grown in the lab for transplantation. The retina has a complicated circuitry comprised of nerve cells that are important for processing visual information into a perceived image.

It is not so simple to transplant an eye or individual cells taken from one eye and place them in another, expecting them to connect up perfectly with all the nerves responsible for normal vision.

For example, there are physical barriers that transplanted rods and cones would have to overcome to position themselves in the right place and connect with nerves in the host retina.

The disease processes that lead to blindness in the first place may have led to scarring and remodelling of the host retina, so that transplanted cells have nothing left to connect with.

It is easier to transplant other cell types in the eye that do not have these issues, like retinal pigment epithelial cells (RPE) which can also be grown from hESCs and iPSCs in the lab.

RPE cells are positioned next to the rod and cone photoreceptors, but they are not involved in the complicated circuitry of the retina. Their role is to supply nutrients to the photoreceptors, take away waste products, and recycle light sensitive molecules.

Some common causes of blindness, like age-related macular degeneration, are actually diseases of the RPE – photoreceptors get damaged as bystanders to the inflammation and bleeding that occur.

That is why clinical trials testing the efficacy of stem cell therapies are transplanting RPE cells and not photoreceptors. So far, the results seem promising and the transplantation of RPE cells appears to be safe.

in aug 2021

Scientists have managed to nurture small clumps of the human brain, giving them the ability to grow their own eyes, or at least two functionally integrated optic vesicles that respond to light.

April 13 , 2022

There are still numerous obstacles to overcome before lab-grown eyes may be used for transplantation. The retina comprises a complex circuitry made up of nerve cells that is responsible for converting visual data into perceptible images.

Transplanting an eye or individual cells from one eye into another and expecting them to connect flawlessly with all of the nerves necessary for normal vision is not straightforward.

So far, the results are encouraging, and RPE cell transplantation appears to be a safe procedure. Therefore, it’s not too far away when we may be able to grow “an eye in a dish” and transplant it to restore a blind person’s vision!

As of nov 2022

The focus is on usher syndrome

The genetic condition in question here is Usher syndrome, a rare birth defect that can leave a baby born deaf and with eyesight that degenerates by adulthood. By growing mini eyes from donors with and without Usher syndrome, the team was able to observe differences between the two. This could ultimately lead to clues for new treatments for the disease, as well as others like retinitis pigmentosa.

January 11, 2023 (this article)

"We wanted to use the cells from those organoids as replacement parts for the same types of cells that have been lost in the course of retinal diseases," says Gamm.

"But after being grown in a laboratory dish for months as compact clusters, the question remained – will the cells behave appropriately after we tease them apart? Because that is key to introducing them into a patient's eye."

"We've been quilting this story together in the lab, one piece at a time, to build confidence that we're headed in the right direction," says Gamm, from the University of Wisconsin-Madison.

"It's all leading, ultimately, to human clinical trials, which are the clear next step."

Further analysis revealed that the cell types that were most commonly forming synapses were the photoreceptors, commonly distinguished as rods and cones. That's encouraging, because these cell types are the ones lost in diseases such as retinitis pigmentosa and age-related macular degeneration.


Edit: before people ask "why they are focusing on genetic defects rather than entirely focusing on growing eyes in lab?"

My understanding is:

They are trying to fix the smaller problems and then move on to the bigger ones, this makes it more sustainable and proves the technology is safe.

They also need more funds in order to continue their research.

The harder problems you try to fix the more investments are required.