Scientists have finally figured out ‘exactly where plaques rupture’ and an enzyme associated with it could be used to predict future cardiovascular disease and develop better treatments for stroke and myocardial infarction

A leading contributor to both myocardial infarction and stroke is the bursting of atherosclerotic plaques. The specific location of such ruptures has been elusive in the past, but scientists from Lund University have now successfully pinpointed this.

Moreover, the team of researchers has singled out an enzyme marker that they believe could be instrumental in determining individuals at risk of myocardial infarction or stroke triggered by a burst atherosclerotic plaque.

Atherosclerosis refers to a condition where fat deposits accumulate within the arterial walls, leading to the formation of atherosclerotic plaques. Rupturing of these plaques can trigger a stroke or myocardial infarction, necessitating a better comprehension of the mechanisms governing plaque rupture to mitigate severe health consequences.

New findings from Lund University in Sweden demonstrate that atherosclerotic plaques in the carotid arteries are prone to rupture at the plaque’s commencement, specifically the point nearest to the heart.

This study has been published in the Journal of the American College of Cardiology (JACC).

“In our study, we were able to pinpoint exactly where plaques rupture,” remarks lead author Isabel Goncalves.

“This is an important step, allowing for a better understanding of why they rupture. Previous studies have focused more on how plaques are formed while we have studied the precise area where they rupture, which no previous human study has done.”

The investigation centers around the analysis of atherosclerotic plaques in the carotid arteries of 188 participants. To accurately pinpoint the predominant rupture sites in these plaques, researchers employed sophisticated techniques such as electron microscopy and RNA sequencing. Recognizing that elevated blood pressure and type 2 diabetes amplify the likelihood of atherosclerosis, the study also incorporated these patient groups.

“One of the strengths of our study is that it’s based on a close collaboration between clinically active researchers and experts in bioinformatics. We have also used several different techniques to allow as detailed analyses as possible. It was important to us to include people with type 2 diabetes in the study as this is a group with high risk of dying from complications related to atherosclerosis compared to the rest of the population,” adds first author Jiangming Sun.

RNA sequencing indicated a substantial correlation between the enzyme MMP-9 and the region susceptible to plaque rupture. Elevated MMP-9 levels could also be linked to a heightened probability of subsequent cardiovascular disease in individuals suffering from atherosclerosis. The team of scientists is optimistic about leveraging MMP-9 as an indicator to forecast patients who might be in danger of experiencing a myocardial infarction or a stroke. Additionally, they are exploring the potential to devise novel therapeutic strategies that diminish the risk associated with plaque rupture.

The findings of the study show “that MMP-9 is a marker of future cardiovascular complications,” points out the lead author.

In further studies, they “want to investigate if it’s possible to inhibit the enzyme, so it becomes less active and thus prevent plaque rupture. However, it’s important that such treatment does not lead to unwanted side effects as the enzyme has other important functions in the body.”

For several years, Isabel Goncalves and her clinical research partner, Andreas Edsfeldt, both based at Lund University and practicing physicians at Skåne University Hospital, have been striving to deepen their understanding of plaque ruptures. As clinicians, they encounter a significant number of patients whom they wish they could have intervened with earlier than currently feasible.

“We see a lot of patients who have had a heart attack or have become partially paralysed following a stroke and can no longer live life as they used to. Often, atherosclerosis does not cause symptoms at an early stage so it can take years before the disease is noticed. Sadly, those of us who work clinically discover the plaque too late, when it has already ruptured and caused serious complications like sudden death, heart attack or a stroke. If we can learn more about the underlying mechanisms, we can initiate preventive measures or treat the dangerous plaques in time,” adds Isabel Goncalves. 

Source: 10.1016/j.jacc.2023.04.008 

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