Newswise — The rupture of atherosclerotic plaques often leads to myocardial infarction and stroke. While the precise site of plaque ruptures was previously unclear, Lund University researchers have now charted it. Additionally, the team has pinpointed an enzyme, a marker, which they anticipate could aid in predicting individuals prone to myocardial infarction or stroke resulting from a ruptured atherosclerotic plaque.
In the condition of atherosclerosis, lipids accumulate within arterial walls, forming atherosclerotic plaques. Ruptured plaques pose the risk of stroke or myocardial infarction, highlighting the importance of comprehending the mechanisms behind such ruptures to avert severe consequences. Recent findings from Lund University in Sweden reveal that atherosclerotic plaques frequently rupture at the initial section of the plaque, nearest to the heart. This study has been published in the Journal of the American College of Cardiology (JACC).
"Through our research, we achieved precise localization of plaque ruptures, a significant advancement that enhances our comprehension of the underlying causes. While earlier studies primarily concentrated on plaque formation, our investigation delved into the specific site of rupture, which had not been explored in previous human studies," explains Isabel Goncalves, the lead researcher of the study.
Important patient groups
Isabel Goncalves, the study's lead researcher, holds the position of Professor of Cardiology at Lund University and serves as a senior consultant at Skåne University Hospital (SUS) in Sweden. The research conducted involved an examination of atherosclerotic plaques in the carotid arteries taken from 188 individuals. To obtain a comprehensive understanding of the primary site of plaque ruptures, the researchers employed electron microscope and RNA sequencing techniques. As high blood pressure and type 2 diabetes are known risk factors for atherosclerosis, individuals with these conditions were also included in the study.
"The strength of our study lies in the close collaboration between clinically active researchers and bioinformatics experts. By employing multiple techniques, we ensured detailed analyses of the data. The inclusion of individuals with type 2 diabetes was particularly important, as this group faces a higher risk of succumbing to complications related to atherosclerosis when compared to the general population," explains Jiangming Sun, a bioinformatics researcher at Lund University and the first author of the published paper.
Marker for complications
The RNA sequencing analysis revealed a significant correlation between the enzyme MMP-9 and the specific region of plaque rupture. Elevated levels of MMP-9 may indicate a heightened risk of developing cardiovascular diseases in individuals with atherosclerosis. The researchers aim to utilize MMP-9 as a potential marker for predicting the susceptibility of patients to myocardial infarction or stroke. Additionally, they are exploring the feasibility of developing novel treatments that can mitigate the risk of plaque rupture.
"Our study demonstrates that MMP-9 serves as a predictive marker for future cardiovascular complications. In subsequent investigations, our focus will be on exploring the feasibility of inhibiting the activity of this enzyme to prevent plaque rupture. Nonetheless, it is crucial to ensure that any treatment targeting MMP-9 does not result in unintended side effects, considering its other vital functions within the body," emphasizes Isabel Goncalves.
Preventive measures
Over the course of several years, Isabel Goncalves, along with her clinically active research colleague Andreas Edsfeldt, who is both a physician at Skåne University Hospital and affiliated with Lund University, has dedicated their efforts to deepen the understanding of plaque rupture. As medical practitioners, they encounter numerous patients whom they aspire to assist at an earlier stage than currently feasible. Their collaborative research endeavors aim to bridge this gap and offer improved interventions for individuals at risk of plaque rupture-related complications.
"We frequently encounter patients who have suffered a heart attack or experienced partial paralysis resulting from a stroke, significantly impacting their quality of life. Atherosclerosis often remains asymptomatic during its early stages, leading to a delayed diagnosis that may take years. Regrettably, as clinicians, we often identify the plaque when it has already ruptured, causing severe complications such as sudden death, heart attacks, or strokes. By deepening our understanding of the underlying mechanisms, we can proactively implement preventive measures or intervene in a timely manner to address these hazardous plaques," expresses Isabel Goncalves.
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