Category: Cardiovascular Disease

Despite Heart Failure Improvement, Continued Medication is Important

Photo by Towfiqu Barbhuiya on Unsplash

Patients who have been treated for heart failure and experience an improvement of their pump function, are still at higher risk of heart-related death or hospitalisation if they stop taking heart failure medications. This is according to a new study from Karolinska Institutet published in Circulation.

“Our finding raises awareness about the importance of implementing and not withdrawing medical treatments in daily clinical practice even if patients with heart failure experience an improvement in symptoms and pump function,” says the study’s last author Gianluigi Savarese, docent and senior lecturer at the Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, and senior cardiologist at Södersjukhuset. 

Using data from the Swedish Heart Failure Registry, RiksSvikt, the researchers have analysed more than 8700 patients with heart failure whose heart pump function, the ejection fraction, was initially impaired (below 40%) but later improved to 40% or more.  

By linking RiksSvikt with other national registers, the researchers from Karolinska Institutet and Linköping University, Sweden, and the University of Naples, Italy, among others, were able to track hospitalisations and deaths in patients who stopped or continued various heart failure treatments. 

Increased morbidity and mortality 

The observational study shows that patients who stopped taking medication of the type RASi (renin-angiotensin system inhibitors), ARNi (angiotensin receptor-neprilysin inhibitors) or MRA (mineralocorticoid receptor antagonists) had between 36 and 38% higher risk of heart-related death or hospitalisation within one year of medication discontinuation.  

However, stopping beta-blocker medication was only associated with a higher risk in patients whose heart function had only moderately improved. 

“Our results show that heart failure medications continue to provide important benefits even when heart function has improved,” says Gianluigi Savarese. “This supports the current recommendation to continue with RASi/ARNi and MRA treatment, but also opens up the possibility of reconsidering whether beta-blockers can be discontinued in certain patients whose heart function has recovered well.” 

More tailored treatment strategies 

Since it was an observational study, no firm conclusions can be drawn about causality. It cannot be ruled out that the results were influenced by residual confounding. The researchers are now planning further studies to confirm the results. 

“Our goal is to understand how heart failure medications affect patients with improved heart function and to develop guidelines for when/if it is safe to discontinue certain treatments. This can lead to more tailored and effective treatment strategies for heart failure patients,” says Christian Basile, the study’s first author and PhD student in Gianluigi Savarese’s research group.  

Source: Karolinska Institutet

Substantially Higher Risk of Heart Attack in Cannabis Users

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Marijuana is now legal in many places, but is it safe? Two new studies add to mounting evidence that people who use cannabis are more likely to suffer a heart attack than people who do not use the drug, even among younger and otherwise healthy adults. The findings are from a retrospective study of over 4.6 million people published in JACC Advances and a meta-analysis of 12 previously published studies being presented at the American College of Cardiology’s Annual Scientific Session.

Marijuana use has risen in the United States, especially in states where it is legal to buy, sell and use the drug recreationally. In the retrospective study, researchers found that cannabis users younger than age 50 were over six times as likely to suffer a heart attack compared to non-users. The meta-analysis, which is the largest pooled study to date examining heart attacks and cannabis use, showed a 50% increased risk among those who used the drug.

“Asking about cannabis use should be part of clinicians’ workup to understand patients’ overall cardiovascular risk, similar to asking about smoking cigarettes,” said Ibrahim Kamel, MD, clinical instructor at the Boston University Chobanian & Avedisian School of Medicine and internal medicine resident at St. Elizabeth Medical Center in Boston and the study’s lead author. “At a policy level, a fair warning should be made so that the people who are consuming cannabis know that there are risks.”

Kamel and his team conducted the retrospective study using data from TriNetX, a global health research network that provides access to electronic medical records. Their findings indicate that over an average follow-up of over three years, cannabis users had more than a sixfold increased risk of heart attack, fourfold increased risk of ischaemic stroke, twofold increased risk of heart failure and threefold increased risk of cardiovascular death, heart attack or stroke. All study participants were younger than age 50 and free of significant cardiovascular comorbidities at baseline, with blood pressure and low-density lipoprotein (LDL) cholesterol levels within a healthy range and no diabetes, tobacco use or prior coronary artery disease.

For the meta-analysis, the researchers pooled data from 12 previously published research studies that collectively included over 75 million people. The studies were rated as being of moderate to good quality in terms of methodology. Of the 12 studies, 10 were conducted in the United States, one in Canada and one in India. Some of the studies did not include information about participants’ ages, but the average age was 41 years among those that did, suggesting that the pooled sample reflected a relatively young population.

Taken individually, seven of the studies found a significant positive association between cannabis use and heart attack incidence, while four showed no significant difference and one showed a slightly negative association. When the researchers pooled the data from all studies and analysed it together, they found a significant positive association, with active cannabis users being 1.5 times as likely to suffer a heart attack compared with those who aren’t current users.

Cannabis use and heart attack incidence was assessed in a similar manner across the different studies. However, due to inconsistencies in the data available from each study, researchers were unable to account for several potential confounding factors including the duration and amount of cannabis use or the use of tobacco or other drugs. 

“We should have some caution in interpreting the findings in that cannabis consumption is usually associated with other substances such as cocaine or other illicit drugs that are not accounted for,” Kamel said. “Patients should be forthcoming with their doctors and remember that we are their number one advocate and having the full story matters.”

While the mechanisms through which marijuana or its components may impact the cardiovascular system are not fully understood, the researchers hypothesize that it can affect heart rhythm regulation, heighten oxygen demand in the heart muscle and contribute to endothelial dysfunction, which makes it harder for the blood vessels to relax and expand, and can interrupt blood flow. One of the studies included in the meta-analysis found that the risk of heart attack peaked about one hour after marijuana consumption.

Since both studies were limited by their retrospective nature and the meta-analysis was limited by the challenges inherent in pooling data from multiple studies, researchers said that additional prospective studies would help to confirm the findings and determine which groups may face the highest risk. 

A previous study presented at the American College of Cardiology’s Annual Scientific Session in 2023 found that daily marijuana use was associated with an increased risk of developing coronary artery disease. 

The retrospective analysis will simultaneously publish in JACC Advances.

Source: American College of Cardiology

Breakthrough Research Offers Hope for Ischaemic Heart Failure

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

Researchers report a groundbreaking discovery in cardiac regeneration that offers new hope for the treatment of ischaemic heart failure. Published in npj Regenerative Medicine, the study reveals a novel approach to promoting cardiomyocyte proliferation.

The paper was authored by researchers at Baylor College of Medicine, the QIMR Berghofer Medical Research Institute in Brisbane, Australia, and collaborating institutions.

“When the heart cannot replace injured cardiomyocytes with healthy ones, it becomes progressively weaker, a condition leading to heart failure. In this study, we investigated a new way to stimulate cardiomyocyte proliferation to help the heart heal,” said co-corresponding author Dr Riham Abouleisa, assistant professor in the Division of Cardiothoracic Surgery at Baylor.

Previous studies showed that calcium plays an important role in cardiomyocyte proliferation. In the current study, Abouleisa and her colleagues explored how modulating calcium influx in cardiomyocytes would affect their proliferation.

“We found that preventing calcium influx in cardiomyocytes enhances the expression of genes involved in cell proliferation,” Abouleisa said. “We prevented calcium influx by inhibiting L-Type Calcium Channel (LTCC), a protein that regulates calcium in these cells. Our findings suggest that LTCC could be a target for developing new therapies to induce cardiomyocyte proliferation and regeneration.”

The study demonstrates that both pharmacological and genetic inhibition of LTCC can induce cardiomyocyte replication and that this occurs by modulating the activity of calcineurin, a known regulator of cardiomyocyte proliferation. This innovative approach showed promising results both in human cardiac slices grown in the lab and in live animals.

Abouleisa and her colleagues’ research highlights the importance of targeting calcium signalling pathways to unlock the regenerative potential of the heart and opens new avenues for developing cardiac regenerative therapies, potentially transforming the treatment landscape for patients suffering from heart failure.

Source: Baylor College of Medicine

In Younger Women, Stress is Associated with an Increased Stroke Risk

Credit: American Heart Association

Some people living with chronic stress have a higher risk of stroke, according to a study published on online in Neurology®, the medical journal of the American Academy of Neurology. The study looked at younger adults and found a correlation between stress and stroke, with no known cause, in female participants, but not male participants.

“Younger people often experience stress due to the demands and pressures associated with work, including long hours and job insecurity, as well as financial burdens,” said Nicolas Martinez-Majander, MD, PhD, of the Helsinki University Hospital in Finland.

“Previous research has shown that chronic stress can negatively affect physical and mental health. Our study found it may increase the risk of stroke in younger women.”

For the study, researchers looked at 426 people aged 18 to 49 who had an ischaemic stroke with no known cause. They were matched for age and sex with 426 people who did not have stroke. Participants completed a questionnaire about stress levels over a one-month period. Those with stroke were asked after their stroke to record stress levels in the month prior to their stroke.

Participants were asked 10 questions, such as “In the last month, how often have you felt that you were unable to control the important things in your life?” Scores for each question ranged from zero to four, with four meaning “very often.” A total score of 0 to 13 represented low stress; 14 to 26, moderate stress; and 27 to 40, high stress.

Those with stroke had an average score of 13 compared to those without stroke who had an average score of 10. People with stroke were more likely to have at least moderate stress levels. Of those with stroke, 46% had moderate or high stress levels compared to 33% of those who did not have stroke. After adjusting for factors that could affect risk of stroke such as education level, alcohol use and blood pressure, researchers found for female participants, moderate stress was associated with a 78% increased risk of stroke and high stress was associated with a 6% increased risk.

Researchers did not find a link between stress and stroke in male participants. “More research is needed to understand why women who feel stressed, but not men, may have a higher risk of stroke,” said Martinez-Majander.

“In addition, we need to further explore why the risk of stroke in women was higher for moderate stress than high stress. Knowing more about how stress plays a role could help us to create better ways to prevent these strokes.”

A limitation of the study was that people experiencing higher levels of stress may have been less likely to enrol in the study, which could have affected the results.

Source: American Academy of Neurology

New Study Supports Caution on Corticosteroids Use in Lupus Heart Condition

Human heart. Credit: Scientific Animations CC4.0

A new study of more than 2900 patients provides evidence that it’s likely best to use as little corticosteroid medicine as possible when treating people who have lupus pericarditis, a common heart complication of the autoimmune disease Systemic Lupus Erythematosus (SLE).

This study, funded by the National Institutes of Health’s (NIH) National Heart, Lung, and Blood Institute (NHLBI) and led by Johns Hopkins Medicine cardiologists and rheumatologists who led the study say their analysis of data affirms that using steroids to curb heart inflammation and other painful symptoms for lupus patients is also a risk factor for recurring pericarditis,.  

Results of this study were published in JAMA Network Open.

The American Heart Association defines pericarditis as inflammation of the pericardium, the twin-layered sac-like structure surrounds the heart to hold it in place and help protect it. Pericarditis typically presents as chest pain that can be exacerbated by lying flat and improved by leaning forward. This pain can last anywhere from a few days to several months. Treatment options for pericarditis include use of colchicine, an anti-inflammatory medication that prevents the recurrence of pericarditis, and corticosteroids.

Pericarditis occurs in 15% to 30% of patients with SLE, a chronic autoimmune disease that causes the body’s immune system to attack its own tissues. “It is well known that, in the general population, one fifth of patients who experience pericarditis end up experiencing one or more recurrences. Surprisingly, even though pericarditis is the most common cardiac complication of Lupus, we could not find any information on recurrent of pericarditis in this patient population,” says Dr Luigi Adamo, MD, PhD, director of Cardiac Immunology at Johns Hopkins University and co-senior author of this study.

Researchers set out to address this gap in knowledge and examine the risk factors contributing to the recurrence.

For the new analysis, researchers used data gathered among the Hopkins Lupus Cohort, a large ongoing study group that includes information on 2,931 patients diagnosed with SLE between 1988 to 2023 and the investigators focused on data from 590 patients also diagnosed with pericarditis. Pericarditis in the data set was identified using the Safety of Estrogens in Lupus Erythematosus National Assessment – SLE Disease Activity Index (SELENA-SLEDAI), a standard tool in the assessment of SLE clinical activity.   

Study results showed that 20% of patients with Lupus who experienced pericarditis had a recurrence. Recurrent pericarditis was most prevalent among patients within the first year of pericarditis onset, with recurrence decreasing in the following years. Younger patients and those with uncontrolled disease were at greater risk of recurrence. It was noted that oral prednisone therapy, a tool frequently used to treat pericarditis in patients with autoimmune diseases, was associated with a higher chance of pericarditis recurrence in patients with SLE.

“The cardiology literature has shown that use of corticosteroids increases the risk of recurrent pericarditis in the general population. Nevertheless, steroids are very frequently used by rheumatologists to treat lupus pericarditis. Therefore, the findings from this study underscore the importance of minimising oral corticosteroid use in patients with lupus and indicate the need for alternative strategies.” said Andrea Fava, MD, a rheumatologist who specialises in care of patients with lupus and co-senior author of the study.

Source: Johns Hopkins Medicine

New Drug may Delay Need for Aortic Valve Surgeries by Slowing Disease Progression

Artificial heart valve. Credit: Scientific Animations CC4.0

Researchers at Mayo Clinic are exploring the use of a new drug called ataciguat to manage aortic valve stenosis (AVS). Results from preclinical and clinical studies, published in Circulation, show that ataciguat has the potential to significantly slow disease progression. The final step to establish the drug’s long-term effectiveness and safety is a phase 3 trial, and efforts to launch that pivotal trial are soon to be underway with an industry partner.

In AVS, calcium deposits build up and narrow the aortic valve, forcing the heart to work harder to move blood. The condition typically progresses over time, with symptoms like chest pain, shortness of breath and fatigue affecting people over age 65. The current standard of care, watchful waiting, often leads to reduced quality of life before the condition is severe enough for the patient to have a surgical or interventional valve replacement.

“This research represents a significant advancement in the treatment of aortic valve stenosis,” says Jordan Miller, PhD, director of the Cardiovascular Disease and Aging Laboratory at Mayo Clinic.  “Ataciguat has the potential to substantially delay or even prevent the need for valve replacement surgery, significantly improving the lives of millions.”

Dr Miller notes that the impact extends beyond simply delaying surgery. Younger patients with aggressive disease or congenital valve defects may develop symptoms in midlife. If a patient requires valve replacement before the age of 55, there is a more than 50% likelihood they will require multiple valve replacement surgeries over their lifetime due to recalcification of the implanted valve. Ataciguat, which slowed progression of native aortic valve calcification in the clinical trial, offers the potential for a once-in-a-lifetime procedure if they can reach the age of 65. The older a patient is, the less likely the implanted valve is to calcify.

Over the past decade, Mayo Clinic’s research revealed that ataciguat reactivates a pathway crucial in preventing valvular calcification and stenosis. Preclinical studies in mice showed that this drug substantially slowed disease progression even when treatment began after the disease was established.  

Clinical trials in patients with moderate AVS demonstrated that once-daily ataciguat dosing was well tolerated, with minimal side effects compared to placebo. This latest phase 2 trial in 23 patients showed a 69.8% reduction in aortic valve calcification progression at six months compared to placebo, and patients receiving ataciguat tended to maintain better heart muscle function. Crucially, the research team confirmed that, despite its profound effect on slowing valve calcification, ataciguat did not negatively impact bone formation.

Source: Mayo Clinic

New Treatment-resistant Blood-clotting Disorder Identified

Thrombophilia. Credit: Scientific Animations CC4.0.

Researchers at McMaster University have made a groundbreaking discovery in the field of haematology, providing an explanation for spontaneous and unusual blood-clotting that continues to occur despite treatment with full-dose blood thinners.

The discovery, published in The New England Journal of Medicine, is expected to influence how doctors test for, and treat patients with, unusual or recurrent blood clotting, with the potential to improve patient outcomes.

Researchers found this new blood clotting disorder to have certain similarities to vaccine-induced immune thrombocytopenia and thrombosis (VITT) – a rare but aggressive clotting disorder that was caused by certain discontinued COVID-19 vaccines.

The research reveals that certain patients can develop severe blood clotting due to antibodies that closely resemble those that cause VITT, even in the absence of known triggers for such antibodies, such as blood thinners (heparin) or prior vaccination.

The newly identified disorder has been termed VITT-like monoclonal gammopathy of thrombotic significance (MGTS).

“Our study highlights the importance of recognising and diagnosing this new blood-clotting disorder,” said Theodore (Ted) Warkentin, co-first author and corresponding author of the study and professor emeritus in the Department of Pathology & Molecular Medicine at McMaster University.

“By understanding how to diagnose VITT-like MGTS, we can develop more effective treatment strategies that go beyond traditional anticoagulation,” said Warkentin, a hematologist in the Department of Medicine based at Hamilton Health Sciences’ Hamilton General Hospital.

Specialized testing was conducted at the McMaster Platelet Immunology Laboratory within the Michael G. DeGroote Centre for Transfusion Research, the only laboratory in Canada with the full repertoire of testing required to characterize the VITT-like antibodies that target the PF4 protein. Researchers performed a detailed analysis of cases exhibiting unusual blood-clotting despite patients being on full-dose blood thinners, focusing on those patients who had unexplained VITT-like antibodies that were detectable for a year or more.

The analyses identified the presence of M (monoclonal) proteins (which typically indicate plasma cell disorders), and together with the persisting VITT-like reactivities over at least 12 months (which is highly unusual for most anti-PF4 antibodies), thus pointing to an ongoing pathological process rather than a short-term anomaly.

The study included a multinational collaboration, with data collected from five patients treated at institutions in Canada, New Zealand, France, Spain, and Germany.

Collaborator Jing Jing Wang of Flinders University in Australia played a crucial role in proving for each patient that the M proteins are the pathological VITT-like antibodies. Collaborator Andreas Greinacher of Greifswald University in Germany helped in identifying similar cases in his anti-PF4 reference lab.

“The findings of this study underscore our ability to leverage fundamental molecular and biochemical science to unravel disease mechanisms,” said Ishac Nazy, co-lead author of the study and scientific director of the McMaster Platelet Immunology Laboratory and co-director of the Michael G. DeGroote Centre for Transfusion Medicine.

“This approach enables precise patient diagnosis and informs timely treatment strategies, even for previously unidentified diseases, exemplifying true bench-to-bedside translational medicine,” said Nazy, associate professor in the Department of Medicine at McMaster.

A remarkable observation was that each of the patients had failed blood thinning treatment, but they showed some benefit with unusual treatments, such as high-dose intravenous immunoglobulin (IVIG), Bruton tyrosine kinase inhibitors (ibrutinib), and plasma cell–targeted myeloma therapy. The existence of this novel blood clotting disorder has important implications for how health care providers will evaluate patients who develop unusual or difficult to treat blood clots in the future.

Source: McMaster University

Mechanical Heart Valve Replacements have Better Long-term Survival

Artificial heart valve. Credit: Scientific Animations CC4.0

Patients aged between 50 to 70 years with a mechanical heart valve replacement had better long-term survival compared to those with a biological valve, new research led by the University of Bristol has found. The study is published in the European Journal of Cardio-Thoracic Surgery.

The last two decades have seen an increase in the use of biological over mechanical heart valve replacements. However, while short-term clinical outcomes are known to be the same, long-term outcomes are still under debate.

Existing guidelines support the use of mechanical valves made of synthetic materials in patients below the age of 50, while biological valves made of animal tissue are favoured for those above the age of 65 or 70. The guidelines leave the choice to the decision of surgeons and patients who are 50 to 70 years old.

The research team wanted to find out the clinical outcomes for patients aged between 50 to 70 years undergoing elective and urgent heart valve replacement at the Bristol Heart Institute (BHI) over a 27 year period [1996 to 2023].

The researchers also sought to investigate trends, early outcomes and long-term survival rates, the incidence of repeat valve interventions and patient prosthesis mismatch (PPM).

A total of 1708 (61% male) patients with an average age of 63 years were included with 1191 (69.7%) receiving a biological valve replacement.

The research found there were no short-term differences when comparing patients receiving biological and mechanical valves. However, patients who received mechanical valves had better long-term survival up to 13 years after having surgery. 

Patients with a size 19mm biological valve replacement (a fairly small valve commonly used in females) had the worse long-term survival. Patients with a size 21mm mechanical valve had better survival compared to both size 19 and 21mm biological valves.  The study confirmed that severe PPM is a significant risk factor for poor long-term survival.

Gianni Angelini, BHF Professor of Cardiac Surgery at the Bristol Medical School: Translational Health Sciences (THS), Director of the Bristol Heart Institute and corresponding author, said: “Our study has implications for decision-making in surgical heart valve replacements for patients aged between 50 and 70 years old. The evidence supporting better long-term survival in patients receiving a mechanical heart valve suggests the current trend favouring biological valves in this age bracket should be urgently reconsidered. The survival benefit is especially clear in smaller sized valves.”

The research team recommends the evaluation of the long-term benefits associated with mechanical valves, especially in smaller sizes, despite long-term blood thinners not being needed with biological valves.

Study limitations

The single-institution design, retrospective collection of data, and absence of randomisation make the study open to bias. The lack of echocardiographic information could potentially underestimate the incidence of structural valve failure. In terms of repeat valve interventions, only patients who underwent re-do surgical aortic valve replacement or valve in valve transcatheter aortic valve implantation (TAVI) at the BHI were included.

As the BHI is a supra-regional centre, it is very unlikely that many patients might have undergone reintervention in other institutions. The cause of  death (cardiovascular/non cardiovascular) was not available.

Source: University of Bristol

Study Probes How to Predict Complications from Preeclampsia

Data from 8843 women diagnosed with preeclampsia during pregnancy showed that existing risk prediction models are most accurate only in the days after diagnosis

Photo by Shvets Production on Pexels

The existing prediction models for severe complications of preeclampsia are most accurate only in the two days after hospital admission, with deteriorating performance over time, according to a new study published February 4th in the open-access journal PLOS Medicine by Henk Groen of University of Groningen, the Netherlands, and colleagues.

Preeclampsia is a potentially life-threatening condition that can occur during pregnancy; of women diagnosed with preeclampsia, 5-20% will develop severe complications. Two existing PIERS (Pre-eclampsia Integrated Estimate of RiSk) models, PIERS Machine Learning (PIERS-ML) and the logistic-regression-based fullPIERS, are designed to identify individuals at greatest or least risk of adverse maternal outcomes in the 48 hours following hospital admission for preeclampsia. However, both models are regularly used for ongoing assessment beyond the first 48 hours.

In the new study, researchers used data from 8843 women diagnosed with preeclampsia at a median gestational age of 36 weeks between 2003 and 2016. Data included PIERS-ML and fullPIERS assessments as well as health outcomes.

The study found that neither the PIERS-ML nor fullPIERS model maintained good performance over time for repeated risk stratification in women with preeclampsia. The PIERS-ML remained generally good at identifying the very high-risk and very-low risk groups over time, but performance of the larger high-risk and low-risk groups deteriorated significantly after 48 hours. The fullPIERS model underperformed compared to the PIERS-ML model.

“Since there are no better options, clinicians may still use these two models for ongoing assessments after the first admission with pre-eclampsia, but the predictions should be treated with increasing caution as the pregnancy progresses,” the authors say. More prediction models are needed that perform well over time, they add.

The authors add, “Pregnancy hypertension outcome prediction models were designed and validated for initial assessment of risks for mothers; this study shows that such ‘static’ models if used repeatedly over days yield increasingly inaccurate predictions.”

Provided by PLOS

Born to Heal: Why Babies Recover, but Adults scar, After Heart Damage

Photo by William Fortunato on Pexels

Newborns with heart complications can rely on their newly developed immune systems to regenerate cardiac tissues, but adults aren’t so lucky. After a heart attack, most adults struggle to regenerate healthy heart tissue, leading to scar-tissue buildup and, often, heart failure.

A new Northwestern Medicine study in experimental animals reveals a critical difference in how macrophages help repair the heart in newborns versus adults after a heart attack. The study highlights a fundamental difference in how the immune system drives healing based on age.

The study appears in the journal Immunity.

“Understanding why newborns can regenerate their hearts while adults cannot will open the door to developing treatments that could ‘reprogram’ adult macrophages,” said first and co-corresponding author Connor Lantz, lead scientist of the bioinformatics core at the Comprehensive Transplant Center at Northwestern University Feinberg School of Medicine.

In newborns, macrophages perform a process called efferocytosis, which recognizes and eats dying cells. This process triggers the production of a bioactive lipid called thromboxane, signaling nearby heart muscle cells to divide, and allowing the heart to regenerate damaged heart muscle, the study found. In adults, macrophages produce much less thromboxane, leading to a weaker repair signal.

“By mimicking the effects of thromboxane, we might one day improve tissue repair after a heart attack in adults,” Lantz said.

How the study worked

The study examined how the immune system responds to heart injury in mice of different ages, including newborn mice (one day old) and adult mice (eight weeks old). The researchers found the ability of macrophages to engulf dying cells was enhanced in newborn mice due to increased expression of MerTK, a receptor that recognizes dying cells. Therefore, when the scientists blocked this key receptor, newborn mice lost their ability to regenerate their hearts, resembling adult hearts after a heart attack.

Engulfment of dying cells by newborn macrophages triggered a chemical chain reaction that produced a molecule called thromboxane A2, which unexpectedly stimulated heart muscle cells to multiply and repair the damage, the study found. Additionally, nearby muscle heart cells in newborns are primed to respond to thromboxane A2, leading them to change their metabolism to support their growth and healing. But in adults, this process did not work the same way – after an injury, their macrophages did not produce enough thromboxane A2, limiting their ability to regenerate heart tissue.

Source: Northwestern University