Category: Cardiovascular Disease

Categories : Cardiovascular Disease Metabolic DisordersTags :

GLP-1 Drugs Tirzepatide and Semaglutide Provide Protection for Heart Health

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Mass General Brigham researchers used real-world data to conduct a head-to-head study to investigate cardioprotective effects, finding both medications reduced risk.

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A new study from Mass General Brigham provides head-to-head evidence comparing the cardioprotective effects of tirzepatide and semaglutide. The researchers found both medications reduced the risk of heart attack, stroke, and death from any cause. The study is published in Nature Medicine, with results simultaneously presented at the American Heart Association Scientific Sessions 2025.

Previous research shows that semaglutide protects against cardiovascular events like heart attack or stroke. But it wasn’t clear if tirzepatide, also commonly prescribed for type 2 diabetes, has the same cardiovascular benefits.

Researchers used US claims databases to compare the cardiovascular outcomes of nearly one million adults taking tirzepatide, semaglutide, or other medications for type 2 diabetes.

“Randomised controlled trials are often considered the reference standard in the medical evidence generation process. However, not all questions can be answered using this time- and resource-intensive method,” said first author Nils Krüger, MD, a research fellow in the Division of Pharmacoepidemiology and Pharmacoeconomics in the Mass General Brigham Department of Medicine. “Data generated in clinical practice and used secondarily for research allow us to address a wide range of clinically relevant questions time- and resource-effectively – when applied correctly. Moreover, we can study patients who reflect the reality of everyday clinical care, in contrast to the highly selected participants of randomized experiments.”

The study demonstrated a cardiovascular benefit for patients at risk for adverse cardiovascular events who had type 2 diabetes. Compared with sitagliptin, a diabetes drug that has shown neutral effects on cardiovascular outcomes, semaglutide reduced the risk of stroke and heart attack by 18 percent. Treatment with tirzepatide lowered the risk of stroke, heart attack, and death by 13 percent compared to dulaglutide, another GLP-1 receptor agonist that has been available for many years.

“Both drugs show strong cardioprotective effects. Our data also indicate that these benefits occur early, suggesting that their protective mechanisms go beyond weight loss alone,” said Krüger. The exact biological mechanisms underlying these protective effects remain unknown.

Because these medications have only recently become available, studies confirming their cardioprotective mechanisms – particularly those directly comparing the two dominant GLP-1 agents, tirzepatide and semaglutide – are still lacking.

“According to recently presented database analyses by the respective manufacturers, each company’s own drug appears to reduce cardiovascular risk much more effectively than the competitor’s,” said Krüger. “However, our study found only small differences between tirzepatide and semaglutide in cardiovascular protection among populations at risk of adverse events, underscoring that both agents provide protective benefit and could be integrated into clinical cardiovascular practice.”

“We hope that our study will help clinicians better understand how these new medications work in clinical practice. Our transparent and open science practices, including pre-registration of a public protocol and shared analytic code, are designed to support scientific discussion,” said last author Shirley Wang, PhD, an associate epidemiologist in the Division of Pharmacoepidemiology and Pharmacoeconomics in the Mass General Brigham Department of Medicine.

Source: Mass General Brigham

Categories : Cardiovascular Disease IT in HealthcareTags :

Study Highlights the Limits of AI in Heart Care

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Human heart. Credit: Scientific Animations CC4.0

There are limits in applying AI to images of the heart, a new study from the Smidt Heart Institute at Cedars-Sinai reveals. The findings were published in the Journal of the American Society of Echocardiography.

Investigators trained multiple artificial intelligence models to read images from echocardiograms, a type of ultrasound test that evaluates the structure and function of the heart. Their goal was to determine whether AI could use these images to calculate measurements like inflammation and scarring that are normally obtained through another, more costly test called cardiac magnetic resonance imaging (CMRI). By examining findings from 1453 patients who had undergone both tests, they found the AI models could not accomplish this task.

“As compared to echocardiograms, cardiac MRI machines are expensive and not available for many patients, especially those in rural areas, so we had hoped that AI could reduce the need for it,” said Alan Kwan, MD, assistant professor in the Department of Cardiology in the Smidt Heart Institute at Cedars-Sinai and co-senior author of the study. “Our results showed the limited powers of AI in this area.”

Source: Cedars-Sinai Medical Center

Categories : Cardiovascular Disease Metabolic DisordersTags :

Waist-to-Height Ratio Better than BMI at Predicting Cardiovascular Risk

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Photo by Andres Ayrton on Pexels

The ratio of a person’s waist measurement compared to their height is more reliable than body mass index (BMI) at predicting heart disease risk, according to new research from UPMC and University of Pittsburgh physician-scientists. 

This finding, published out now in The Lancet Regional Health—Americas, could reshape how clinicians and the public assess cardiovascular risk, especially for people who don’t meet the classic definition of obesity. 

The team analysed data from 2721 adults who had participated in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). The individuals had no cardiovascular disease at baseline and were followed for more than five years. 

“Higher BMI, waist circumference and waist-to-height ratio at baseline were all associated with higher risk of developing future cardiovascular disease – until we adjusted for other classic risk factors, such as age, sex, smoking, exercise, diabetes, hypertension and cholesterol,” said lead author Thiago Bosco Mendes, clinical instructor of medicine at Pitt and obesity medicine fellow at UPMC. “When we did that, only waist-to-height ratio held as a predictor.” 

Much of that predictive power is concentrated among individuals with a BMI under 30, which is below the classic threshold for obesity, who may not realise they are at risk for cardiovascular disease.  

BMI doesn’t account for fat distribution or distinguish between harmful, visceral fat and protective, subcutaneous fat. By contrast, waist-to-height ratio (WHtR), calculated by dividing waist circumference by height, directly reflects central obesity, which is more closely linked to heart disease. That means that people with a BMI lower than 30, but a WHtR over 0.5, may be at higher risk of future coronary artery calcification, a key marker of cardiovascular disease, even in the absence of other risk factors. 

“Using waist-to-height ratio as a cardiovascular screening tool could lead to earlier identification and intervention for at-risk patients who might otherwise be missed,” said senior author Marcio Bittencourt, associate professor of medicine at Pitt and cardiologist at UPMC. “It’s a simple and powerful way to spot heart disease risk early, even if a patient’s weight, cholesterol and blood pressure all seem normal.” 

Source: University of Pittsburgh School of Medicine

Categories : Cardiovascular DiseaseTags :

Stem Cell Therapy Linked to Lower Risk of Heart Failure After a Heart Attack

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Technique may be a valuable add-on procedure for patients with weak heart function after a heart attack, say researchers

Right side heart failure. Credit: Scientific Animations CC4.0

Patients with weak heart function who receive stem cell therapy shortly after a heart attack are at lower risk of developing heart failure and related hospital stays compared with standard care, finds a clinical trial published by The BMJ.

The researchers say the findings suggest this technique may be a valuable add-on procedure for this particular group of patients after a heart attack to prevent subsequent heart failure and reduce the risk of future adverse events.

Advances in heart attack management have improved survival rates considerably, but this has also led to rising rates of subsequent heart failure. While recent studies have indicated that stem cell therapy may reduce rates of heart failure after a heart attack, clinical trials are needed to confirm these benefits.

To address this gap, the researchers set out to assess the impact of delivering stem cells directly into coronary arteries (known as intracoronary infusion) after a heart attack on the development of heart failure over three years.

Their findings are based on 396 patients (average age 57-59 years) with no previous heart conditions at three teaching hospitals in Iran. They had all experienced a first heart attack (myocardial infarction) leading to extensive heart muscle damage and weakened heart function – where the left ventricle, the heart’s main pumping chamber, is too weak to pump blood out to the body as effectively as it should.

Of these, 136 patients in the intervention group received an intracoronary infusion of allogenic Wharton’s jelly derived mesenchymal stem cells within 3-7 days of their heart attack in addition to standard care. The remaining 260 control group patients received standard care alone.

Factors such as age, sex, baseline heart function, smoking status, obesity, existing high blood pressure, diabetes, or kidney problems were taken into account, and patients were monitored for an average of 33 months.

Compared with the control group, intracoronary infusion of stem cells was associated with reduced rates of heart failure (2.77 vs 6.48 per 100 person years), readmission to hospital for heart failure (0.92 vs 4.20 per 100 person years), and a combined measure of cardiovascular death and readmission for heart attack or heart failure (2.8 vs 7.16 per 100 person years).

The intervention did not have a statistically significant effect on readmission to hospital for heart attack (1.23 vs 3.06 per 100 person years), death from any cause (1.81 vs 1.66 per 100 person years), or cardiovascular death (0.91 vs 1.33 per 100 person-years).

However, by six months heart function in the intervention group showed a significantly greater improvement from baseline at six months compared with the control group.

This was a large trial with long term follow-up and clinically meaningful outcome measures, but the researchers acknowledge several limitations to their findings. These include the inability to do a sham procedure for the control group, which would have allowed for a double blinded study design instead of a single blinded format. Nor did they assess heart failure biomarkers or investigate the physiological effects of the intervention on heart tissue.

Nevertheless, they say these results suggest that this technique “may serve as a valuable adjunctive procedure after myocardial infarction to prevent the development of heart failure and reduce the risk of future adverse events.”

Additional trials confirming this finding are needed as well as further research “to explore the underlying mechanisms of mesenchymal stem cells therapy and to optimise its application in clinical practice,” they add.

Source: BMJ Group

Categories : Cardiovascular Disease Emergency MedicineTags :

Innovative UK Project to Test Drones for Cardiac Arrest Response

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Credit: University of Surrey

A project to test how drones can be integrated into the UK’s 999 emergency response system to rapidly deliver defibrillators to patients experiencing out-of-hospital cardiac arrest (OHCA) has been launched by the University of Surrey, Air Ambulance Charity Kent Surrey Sussex, South East Coast Ambulance Service NHS Foundation Trust. 

With survival rates for OHCA in the UK currently below 10%, a key challenge is the delay in delivering life-saving defibrillation. While public Automated External Defibrillators (AEDs) are widely available, getting them to a patient in time is often difficult. This 16-month project will explore using drones to rapidly deliver AEDs to the scene of an emergency. 

This research is the first step towards integrating drone technology into our emergency response systems. Our ultimate goal is to develop and test the procedures needed to seamlessly introduce drone delivery of AEDs into the 999-emergency system 

Dr Scott Munro, Lecturer in Paramedic Practice at the University of Surrey and co-lead on the project

The initiative, which has been funded by the National Institute for Health and Care Research (NIHR), will be divided into two sections: in the first, researchers will develop and refine the drone delivery process through a series of simulations, coordinating 999 call taking, Air Traffic Control, ambulance dispatch and drone operators.  

In the second part, interviews will be conducted with a diverse group of people -including OHCA survivors, family members, responders and members of the public – to understand the public’s perception of drone technology, including any barriers or concerns, and to ensure ease of use for responders. 

This project is a great example of how NIHR’s RfPB programme supports life-saving innovation. Using drones to deliver defibrillators could help emergency teams reach patients faster, improve survival after cardiac arrest, and bring cutting-edge technology directly to the NHS frontline, while working with the public to ensure it’s used safely and effectively. 

Professor Kevin Munro, Director of the NIHR Research for Patient Benefit (RfPB) Programme

Rapid intervention is vital in managing out-of-hospital cardiac arrests. As demand continues to grow, the opportunity to integrate this technology into future healthcare systems represents real progress in ensuring ambulance services can work with the communities they serve to strengthen the chain of survival and give patients the best chance of a positive outcome Being a partner in this research, we are eager to explore how this new initiative could strengthen our cardiac arrest care pathway. 

Dr Craig Mortimer, Research Manager at South East Coast Ambulance Service NHS Foundation Trust (SECAmb)

Source: University of Surrey

Categories : Cardiovascular Disease RheumatologyTags :

Common Arthritis Drug Reveals Hidden Benefit

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Photo by Towfiqu Barbhuiya on Unsplash

Methotrexate, a common medication used to treat rheumatoid arthritis, has a newly recognised useful secondary effect to lower blood pressure and potentially reduces the risk of heart disease in people with this condition.

A new study, led by Flinders University and Southern Adelaide Local Health Network (SALHN) researchers, has shown that methotrexate significantly lowers blood pressure when compared to another arthritis drug, sulfasalazine. The findings, published in Annals of Medicine, mark the first clear evidence of this effect in newly diagnosed patients.

Occurring in about one in 100 people, rheumatoid arthritis (RA) is a common autoimmune disease which leads to inflammation and pain in the connective tissue of a patient’s joints.

Over six months, the South Australian and Italian researchers followed 62 newly diagnosed adults who had not yet started treatment.

Half were given methotrexate and the other half received sulfasalazine. Researchers then measured their blood pressure, joint inflammation, and stiffness in their arteries at the beginning of the study, then again after one and six months.

Lead author of the study, Professor Arduino Mangoni, from Flinders University’s College of Medicine and Public Health, and SALHN’s Department of Clinical Pharmacology, says they wanted to see if methotrexate could lower systolic blood pressure, which indicates how much pressure your blood is exerting against artery walls when your heart beats.

“We found that methotrexate lowered systolic blood pressure by an average of 7.4mmHg compared with people taking sulfasalazine,” says Professor Mangoni, Strategic Professor of Clinical Pharmacology.

“This kind of reduction is considered meaningful because even a small drop in blood pressure can lower the risk of serious heart problems like heart attacks and strokes.”

Interestingly, this benefit did not seem to be linked to changes in either arthritis symptoms or the stiffness of arteries, suggesting that it might be helping the heart in other ways, like calming inflammation or improving how blood vessels work.

Professor Arduino says the findings are exciting because they show methotrexate might do more than just treat rheumatoid arthritis.

“We’ve known for a while that methotrexate helps with inflammation, but now we’re seeing that it may also help lower blood pressure, which is a major risk factor for heart disease,” he says.

“This could be a big step forward in how we care for people with rheumatoid arthritis.”

The researchers also looked at how genetics might play a role in how well methotrexate works and found that certain genetic traits made some people more likely to experience a drop in blood pressure while taking the drug.

“In short, if someone has specific gene variants, methotrexate might add a heart health benefit to its usual role in treating rheumatoid arthritis by the positive effect on blood pressure,” he says.

The researchers say that this opens the door to more personalised treatment options, where doctors could use genetic testing to predict who might benefit most from methotrexate’s heart-protective effects.

Study coordinator and medical scientist, Dr Sara Tommasi, says that although more research is needed to confirm these findings and understand exactly how methotrexate lowers blood pressure, the results are promising.

“The results suggest that this well-known arthritis drug could also play a role in protecting heart health, especially in people who are at higher risk due to inflammation,” says Dr Tommasi from the College of Medicine and Public Health and South Adelaide Local Health Network.

Source: Flinders University

Categories : Cardiovascular Disease Mental HealthTags :

ED Visits for Low-risk Chest Pain Could be Reduced by Treating Anxiety

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Chest pain ranks as the second most common reason for emergency department (ED) visits, making it a key concern for patients and doctors. However, 80% of these cases are considered low-risk and not related to heart disease, and for these patients, anxiety and panic disorders are frequent diagnoses.

A new study led by the Indiana University School of Medicine and Regenstrief Institute shows that many patients who visit the emergency department (ED) with low-risk chest pain might benefit more from treatment for underlying psychological conditions than from extensive cardiac testing. The study appears in Academic Emergency Medicine.

Anxiety is not only common among low-risk chest pain patients, but is often accompanied by other treatable comorbidities, including depression, somatisation – the experience of psychological distress through physical symptoms – and post-traumatic stress disorder. By identifying and addressing these conditions, more targeted follow-up strategies can be developed to reduce repeat ED visits and unnecessary evaluations, improving patient outcomes and allowing health systems to focus resources where they matter most.

“Anxiety is a common fellow traveller with low-risk chest pain,” said corresponding author, IU School of Medicine and Regenstrief Research Scientist Kurt Kroenke, MD. “It is a frequent issue in the emergency department. While many patients worry about their heart, in many cases the chest pain is not cardiac, which raises the important question of whether there is something else that can be treated.”

The research, part of the Patient-Centered Treatment of Anxiety after Low-Risk Chest Pain in the Emergency Room (PACER) trial, showed that more than 42% of patients had severe anxiety, defined by a score of 15 or higher on the Generalized Anxiety Disorder (GAD-7) scale, a standardised tool developed by Dr Kroenke to assess the severity of anxiety symptoms. In addition, three-quarters of ED patients screened positive for panic disorder.

Evidence-based treatments for anxiety and comorbidities

Researchers identified two effective approaches to reduce anxiety in patients with low-risk chest pain: Cognitive Behavioural Therapy (CBT) and prescription medications. These treatments can be used on their own or combined to create a more comprehensive care plan, helping to better manage symptoms and prevent unnecessary return visits to the ED.

Psychotropic medications such as antidepressants and anti-anxiety medicines remain important tools for managing anxiety disorders. When used appropriately, these medications can lessen both the intensity and frequency of symptoms and are often most effective when paired with psychological therapy.

“There are classes of medicines that are effective for anxiety, particularly when it’s chronic,” said Dr Kroenke. “It’s no different than taking a medicine for high blood pressure – if someone has high blood pressure, we have medicines that lower it. Similarly, if someone has high anxiety, we have medicines that can effectively reduce it.”

The other effective approach is CBT, which helps individuals recognize and reframe thought patterns, manage panic symptoms and reduce fear associated with chest discomfort. Research shows that even brief courses of this behavioral therapy can significantly improve anxiety and quality of life. The PACER trial is comparing standard therapist-administered CBT to peer-supported internet-based CBT in patients with LRCP and anxiety.

“Emergency physicians often reassure patients that their chest pain isn’t caused by the heart, but reassurance alone is not enough. Connecting patients with proven therapies like cognitive-behavioural therapy and medications can change the trajectory of their care and improve long-term outcomes,” said IU School of Medicine and Regenstrief Researcher Paul Musey, MD, MS.

Source: Regenstrief Institute

Categories : Cardiovascular DiseaseTags :

Semaglutide and Tirzepatide Reduce Heart Failure Risk by More than 40%

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Right side heart failure. Credit: Scientific Animations CC4.0

Treatment with semaglutide or tirzepatide can reduce health risks for patients with heart failure by more than 40%. These finding come from a study by researchers at the Technical University of Munich (TUM). The medication can drastically reduce the risk of being hospitalised for heart failure or dying.

Semaglutide and related medications are widely used to treat diabetes and obesity. Their potential effects beyond weight loss are now being closely studied. Still, professional societies and regulatory authorities have urged caution. With regard to treating heart failure, cardiology societies have noted that the existing evidence base remains limited.

“Together with our colleagues at Harvard Medical School, we have created a solid evidence base for using these weight-loss medications in heart failure,” says Professor Heribert Schunkert, Director of the Department of Cardiovascular Diseases at the TUM University Hospital German Heart Center. “In patients with heart failure with preserved ejection fraction, both drugs have shown a clear protective effect that supports their use. Our analysis of around 100 000 patients provides a robust basis for reassessing an indication expansion and new indication approval in heart failure.“

The study focused on heart failure with preserved ejection fraction or HFpEF, in which the heart’s ability to pump remains intact but the stiffened heart muscle does not fill properly with blood. HFpEF affects more than 30 million people worldwide. To date, there are only a few effective treatment options for this form of the disease.

Large-scale database study provides solid evidence for use in heart failure

Published in JAMA, the study examined the effects of the drugs semaglutide and tirzepatidein patients with this specific form of heart failure. The researchers analysed three national US insurance claims databases. Their models first confirmed findings from earlier trials in patients with obesity or diabetes, then extended the analysis to populations excluded from clinical trials and to additional outcomes, such as hospitalisation for heart failure and mortality.

Treatment with both drugs led to a more than 40% reduction in the risk of hospitalisation for heart failure or death compared with another diabetes drug that had shown no effect on heart failure outcomes in previous studies.

“Currently, HFpEF can be treated with a few drugs only. At the same time, an increasing number of patients suffers from obesity and diabetes, which further worsens outcomes. In Germany, heart failure is the leading cause for hospitalizations and a major driver of health care expenditure. Our study shows that these drugs are highly effective, which expands treatment options and could prevent many hospital admissions,” says Dr Nils Krüger, resident physician at the TUM University Hospital German Heart Center and lead author of the study.

Data-driven approaches to drug approval

The study drew on patient populations nearly 20 times larger than those in traditional clinical trials. This allowed researchers to capture clinical practice and demonstrate that the benefits seen in pivotal trials also apply to broader patient groups. “The future belongs to such data‑driven approaches – alongside traditional trials, they can help ensure that findings from basic research feed into patient care more quickly,” explains Prof Schunkert.

From the researchers’ perspective, such analyses are also becoming increasingly relevant for Germany. The Health Data Utilization Act provides that anonymized health insurance data will in future be made systematically available for such research projects, while strictly protecting sensitive personal data. “We use these large data to investigate the safety and effectiveness of medications in clinical practice,” says Dr Krüger.

Source: Technical University Munich

Categories : Cardiovascular Disease NeurologyTags :

Landmark Study Finds Perispinal Etanercept of No Benefit to Stroke Trial Participants

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A treatment for stroke patients was no more effective than an inactive drug

Source: CC0

The first international trial of an unproven stroke treatment available in the US has concluded that, while harmless, perispinal etanercept is no more effective than an inactive dummy drug, or placebo.

Survivors of stroke have travelled at considerable expense to private clinics in the US to be treated with the arthritis drug etanercept.

In the clinics, the drug is injected into the cervical spinal area, and the patient is then tilted head-down in the belief that this allows the drug to enter the brain.

Stroke is a leading cause of disability throughout the world, affecting more than 7 million people a year. Despite advances, treatments for impairment after stroke remain limited. Some patients call perispinal etanercept a “miracle cure”.

Florey leading stroke researcher, neurologist Professor Vincent Thijs led the Perispinal Etanercept to improve STroke Outcomes – or “PESTO” – trial to investigate this further, supported by funding from the Australian Government.

“We understand why people living with the long-term effects of stroke seek hope and new options,” Professor Thijs said. “With support from the Stroke Foundation and the Medical Research Future Fund, we put this treatment to the test using the gold standard of clinical research – a double-blind randomised trial.”

Half of the PESTO participants were treated with the drug, and half were treated with an inactive dummy drug, with patients and doctors “blind” to who was getting which.

This type of trial eliminates biases because neither doctors nor patients knew who was getting etanercept and who was getting the placebo. Because the results for the 2 patient groups were so similar, we concluded that while the drug did not cause harm, we found no evidence that it led to improved quality of life compared to placebo.

Professor Thijs, who leads the Young Stroke Service at The Florey, said improvements could be due to the placebo effect, a well-established medical phenomenon where some patients in a trial may notice an improvement, despite only receiving a dummy treatment.

Key PESTO trial results, published in Neurology:

  • 126 people from Australia and New Zealand participated in PESTO.
  • 63 received the treatment, 63 the placebo.
  • Their stroke symptoms were measured before the trial and 28 days after.
  • There were no adverse side effects.
  • Among participants who received perispinal etanercept, 52 per cent (33 out of 63) felt better.
  • Among participants who received the placebo, 57 per cent (36 out of 63) felt better.
  • The difference in results between the 2 groups is deemed statistically insignificant.

“It’s important for doctors and the stroke survivor community in Australia and around the world to know that we found no evidence that perispinal etanercept improved quality of life,” Professor Thijs said.

Kelvin Hill, Executive Director of Stroke Programs, Research and Innovation at Stroke Foundation said: “Every Australian stroke patient should have access to the best, evidence-based treatment. Findings of the PESTO study underscore the critical importance of robust research and clinical trials in discovering if treatments work or not.

“Australians experience around 46 000 stroke events every year (one every 11 minutes), and there are now over 440 000 survivors of stroke living in Australia. Stroke Foundation will continue to advocate for more research funding to unlock new effective treatments for stroke; and ensure that advice provided in the Living Clinical Guidelines for Stroke Management enables clinicians to provide the best stroke care possible,” Mr Hill added.

Source: Florey Institute of Neuroscience and Mental Health

Categories : Cardiovascular DiseaseTags :

Three-tailed Lipid Molecule Helps Heart and Brain Cells Survive Ischaemia

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Graphical abstract. Chi et al., Journal of the American Chemical Society 2025.

When starved of oxygen during a heart attack or stroke, cells unleash a flurry of emergency measures to protect themselves and the body. For decades, scientists have observed that the body’s production of a “three-tailed” lipid molecule consistently surges during this trauma but have puzzled over why. Now, Cornell researchers have uncovered its surprising role in cellular survival: protecting against damage when oxygen runs out.

The research shows that the fat molecule, N-acylphosphatidylethanolamine (NAPE), helps cells survive ischaemia by driving lactic acid out of cells. This toxic byproduct builds up during emergency metabolism, and NAPE’s surge appears to be part of the body’s protective response. Though still in an early stage, the findings suggest that boosting or mimicking NAPE could one day help limit tissue damage in heart attack and stroke.

The study, published Sept. 5 in the Journal of the American Chemical Society, was led by graduate student Din-Chi Chiu and Jeremy Baskin, associate professor in the Department of Chemistry and Chemical Biology, and the Weill Institute for Cell and Molecular Biology.

“During heart attack or stroke, when there is an interruption in blood flow, the cells in the affected tissue, whether it is the heart or the brain, have to scramble to be able to continue to produce energy to survive,” Baskin said.

Under normal conditions, cells largely produce energy by a longer and much higher yielding process involving mitochondria.

“However, when energy needs are imminent and oxygen is limited, such as when blood flow is restricted, a metabolic switch occurs to favour glycolysis, which is a quick and dirty way of generating energy,” he said. “But to keep glycolysis going unabated, lactate, or lactic acid, is built up, and because it can be toxic at high levels, cells need to export it to prevent it from building up inside cells to undesirable levels.”

Because NAPE repels water and is short-lived in cells, studying it directly has been nearly impossible. The research team overcame this by designing and synthesising a chemical “look-alike” probe that tagged NAPE’s protein partners under UV light, revealing its interactions.

The researchers observed NAPE latching onto proteins that regulate lactate transport. In particular, it bound to two cell-surface proteins, CD147 and CD44, which control transport proteins that act like gates controlling how lactic acid moves in and out of cells. The team’s experiments showed that when NAPE levels rise, lactate transport ramps up, and blocking those transporters erased the effect.

“The work reframes NAPE as a signaling molecule,” Baskin said. “Our finding that NAPE can stimulate lactate export supports a model in which the role of NAPE in pathological events such as heart attack or stroke is part of a protective response.”

For now, the team is exploring whether different versions of NAPE, with different tail compositions, might fine-tune lactate regulation in unique ways. They are also interested in whether NAPE plays roles in other tissues beyond the heart and brain.

“Future studies in heart and brain tissue will test this hypothesis more directly,” Baskin said. “If confirmed, the work could support the creation of therapies that boost NAPE levels as a way to limit tissue damage in cardiovascular emergencies.”

Source: Cornell University