Submitted by Creepy_Toe2680 t3_10sjy8b in Futurology
The following submission statement was provided by /u/Creepy_Toe2680:
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.
Please reply to OP's comment here: https://old.reddit.com/r/Futurology/comments/10sjy8b/heart_disease_breakthrough_new_immune_target/j71p0lp/
Just tell me which supplement to start taking science bitch! /S
You couldnt even make my friend more smarter!
Literally stop eating processed sugar and take a psyllium supplement. Just taking Metamucil without any other changes in your diet will improve your overall heart health.
[removed]
Yay science!
And now I'm including a bunch of completely useless text to satisfy the absurd rule that top level comments much be a certain length. What a dumb idea.
Yup. Cancer survivor. Sugar level is a known problem, and "death starts in the colon." The above is the deal.
I just remember walking out of my Dr.s office, after having been prescribed lipitor for high cholesterol and high BP, and found a tray of pamphlets on heart disease. It described inflamation as the main culprit. Blood overloaded with glucose acts as sandpaper in the arteries, causing inflammation. Cholesterol coats the inflammation and clogs your arteries. Because modern medicine is tuned to treat symptoms instead actual diseases, you end up with drugs like lipitor. Since the behavior that causes the disease is not addressed, drugs will eventually fail. That's across the board for anything that's not genetic. The people that tend to survive are the ones that change behavior and environment. As for gut health, we are slowly but surely finding out how foundational the gut is.
Turn around, I'm your choir. My body has been trying to suicide without permission since I was 39. I've been sick the whole way...but I'm 61 :-)
Amen. Almost the same here.
The finding is that an immune system protein causes the hardening of arteries, not their clogging. Even when you address clogging people are still majorly dying of heart disease. Your point is still valid, that the solution is to treat the disease rather than just throwing drugs at the symptoms.
I am not a doctor and this is not medical advice or approved by the FDA. Someone asked for a supplement to be taking. You have to take large amounts of vitamin K2. While this does not attack the underlying cause (which we knew was inflamation and now appears to be inflammation caused by suPAR) K2 will slowly remove calcium from the atherosclerotic plaque and redeposit it in your bones. It also appears to help stabilize the calcium part of the plaque and helps somewhat to stop the plaque from breaking off and causing heart attacks and strokes. For a numbet of very complex reason (that I'm not going to get into here) most of the plaque is calcium. There are a number of anti-inflammatory supplements but somebody that knows more than I do needs to suggest which one might be better to help counteract suPAR. Everyone older than 35 should be taking an anti-inflammatory and probably several anti-inflammatory supplements as we already knew that inflammatory molecules not only causes atherosclerotic heart disease but it is a major cause of Aging. We did not know the exact mechanism but this paper probably has discovered this mechanism and may lead to the savings of millions of people's lives. Once again we have an effect of aging where in this case, a bad chemical increases as we age and we have to counteract it if we are really going to get serious about extending our lifespan. Heart disease in the US kills over 10,000 people a week and seriously disables at least another 10,000 every week. The worldwide death toll is staggering. Most of the places in the world that they have studied groups of people that live longer do not have heart disease and it is one of the major reasons why they live longer. Maybe there's something in their diet that reduces suPAR? Who knows it could also be genetic? The authors of this paper might be able to get some clues in their development of a anti-suPAR drug by talking to some of the nutritional people that have made these studies of these long lived groups.
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.