A myocardial infarction (MI), or heart attack, doesn’t just damage the cardiovascular system—it can dramatically reshape how the brain functions. A single cardiac event can trigger various neurological effects, from depression and anxiety to different types of cognitive decline.
Now, a new study led by a University of Ottawa team takes a major step forward in answering key questions about how brain function is directly impacted by changes in heart health, a concept referred to as the ‘heart-brain axis.’ It suggests that neurological conditions following a heart attack could be driven in part by molecular changes set in motion by damage to the heart.
While there are many factors and signaling pathways involved in heart-brain interactions, the newly published research suggests that a toxic byproduct produced by the body plays a major role in the brain following a heart attack. This highly compelling finding brings us closer to therapies that could potentially transform recovery and long-term outcomes for millions of people.
What’s behind brain inflammation after cardiac events?
Dr. Erik Suuronen, the study’s senior author, explains that at the center of the discovery is methylglyoxal (MG), a highly reactive molecule. Following a heart attack, the body enters a state of stress—oxygen drops, inflammation rises, metabolism shifts—causing MG levels to surge in the bloodstream and then accumulate in the brain.
“The occurrence of depression and anxiety in heart attack patients is up to three times higher than the general population.”
Dr. Erik Suuronen
Working with a mouse model of human disease, the collaborators found that the “accumulation of this toxic compound in the brain was associated with increased neuroinflammation,” according to Dr. Suuronen. He’s a Full Professor in the Faculty of Medicine’s Department of Surgery, a scientist in the Division of Cardiac Surgery and director of its BEaTs Research Program at the University of Ottawa Heart Institute.
Recently published in the journal Advanced Science, the study revealed that methylglyoxal actually builds up in specific brain regions linked to mood and cognition. This finding could be highly significant, reshaping how scientists understand long-term risks after myocardial infarction and helping to explain why emotional and cognitive disorders are so common after cardiac events.
“Notably, the highest levels of methylglyoxal and inflammation in the brain were observed in regions that are strongly linked to depression and anxiety,” Dr. Suuronen says. “Thus, it is likely that methylglyoxal-mediated damage in the brain contributes to the development of disorders such as depression and anxiety after a heart attack.”
Statistics partially tell the tale of the new work’s potential impact on patients.
“The occurrence of depression and anxiety in heart attack patients is up to three times higher than the general population,” Dr. Suuronen says. “Importantly, patients who suffer depression or anxiety may be up to 2.7 times more likely to experience another heart attack or death.”
Charting new territory in brain-heart connection
The team’s discoveries also raise important questions about neurodegenerative disease.
Chronic inflammation and cellular damage in the brain are key drivers of cognitive conditions like dementia. By identifying methylglyoxal as a trigger, this research suggests a new pathway through which heart attacks could increase long-term neurological risk.
The new study is pioneering in nature. This is the first time scientists have directly shown that MG-derived damage extends into the brain after a heart attack, opening an entirely new area of investigation into heart–brain interactions.
“Methylglyoxal has been widely studied for its role in metabolic diseases, including diabetes, but much less is known about its function in other diseases,” Dr. Suuronen explains. “In a previous study, we discovered that methylglyoxal was produced by dying heart tissue after a heart attack… Based on this evidence, we predicted that methylglyoxal in the blood would target other organs and tissues, including the brain—and this is what we did indeed observe.”
“The highest levels of methylglyoxal and inflammation in the brain were observed in regions that are strongly linked to depression and anxiety.”
Dr. Erik Suuronen
Experiments in this study were led by Ramis Ileri, a PhD student from Turkey who is pursuing his graduate degree in the Ottawa-Carleton Institute for Biomedical Engineering program.
Moving from discovery toward therapy
The publication’s findings point toward a potential solution. Having identified methylglyoxal as a potential target for treating neurological disorders after a heart attack, the next step is to better understand the process, according to Dr. Suuronen.
He says future work will explore how MG-driven inflammation leads to neuron death and mental health conditions. Importantly, the research team has already developed a peptide therapeutic that can trap methylglyoxal and prevent it from damaging cells.
“This therapy will soon be tested to see if it can protect the brain from damage after a heart attack,” he says.
If successful, such treatments could do more than protect brain function; they could potentially reduce the risk of future cardiac events.
“Given the increased risk of subsequent heart attacks or death in heart attack patients who experience depression or anxiety, being able to alleviate these conditions could reduce subsequent major cardiac events and improve the lives of countless patients, filling an urgent unmet clinical need,” Dr. Suuronen says.