Researchers have identified that genetic factors play a significant role in determining the cellular makeup of atherosclerotic plaques. Over time, this can influence the likelihood of these plaques leading to a stroke or heart attack. This important finding could enhance future risk evaluation and treatment strategies for individuals suffering from atherosclerosis.
In a study recently published in the European Heart Journal, investigators from Karolinska Institutet have revealed that genetic characteristics affect the cellular structure of atherosclerotic plaques, which ultimately can influence the risk of experiencing a stroke or heart attack. This insight could pave the way for improved risk assessment and treatment for patients with atherosclerosis moving forward.
Atherosclerosis is the primary cause of cardiovascular diseases, including stroke and heart attack. Researchers from Karolinska Institutet, collaborating with experts from Stanford and Virginia universities in the USA, have managed to uncover the relationship between genetic traits and the types of cells present in atherosclerotic plaques. This research utilized tissue samples from a biobank (Biobank of Karolinska Endarterectomies, BiKE) sourced from patients diagnosed with atherosclerosis.
“Earlier studies indicated that genetics influence cholesterol levels, lipid profiles, and circulating immune cells in the bloodstream, but we’ve now demonstrated that genetics also plays a role in the composition of smooth muscle cells in the blood vessels of atherosclerosis patients,” explains Ljubica Matic, a lecturer at the Department of Molecular Medicine and Surgery at Karolinska Institutet who spearheaded the study. “This can influence how atherosclerotic plaques develop and their propensity to destabilize and potentially lead to a stroke.”
By analyzing genetic data, the research team categorized patients into three distinct groups.
“The first group exhibits the most severe conditions, and many have already experienced a stroke,” notes Ljubica Matic. “The second group is at lower risk, displaying plaque formation in their vessels without having suffered a stroke. The third group lies between these extremes, typically presenting with both kidney disease and atherosclerosis. We also have initial indications that this same principle may apply to heart attacks.”
The insights gained regarding genetic influence on plaque cell composition can be utilized alongside cutting-edge diagnostic imaging and AI technologies. This could lead to enhanced evaluations of future stroke or heart attack risks or predictions on how patients might respond to various medications.
“We’ve conducted similar studies on smaller patient cohorts in prior publications to validate this approach, but this concept needs validation on a larger scale before it becomes part of standard clinical practice,” remarks Professor Ulf Hedin from the same Karolinska Institutet department. “We are committed to advancing these modern, multi-modal studies in the near future through our newly funded EU Horizon 2020 NextGen and MedTechLabs initiatives.”
Atherosclerotic plaques develop over many years as blood lipids, particularly cholesterol, accumulate in the innermost layer of blood vessel walls. When these plaques become unstable and break apart, they can lead to the formation of blood clots, which can obstruct vessels or travel to other organs, such as the brain. Both scenarios can result in tissue oxygen deprivation, potentially causing a heart attack or stroke.
Despite consistent declines in mortality from cardiovascular diseases over the past 50 years—thanks to advancements in understanding these mechanisms, improved preventive care, diagnostics, and healthier lifestyle choices—it remains the leading cause of death in Sweden.
The research received funding from various sources, including the Swedish Research Council, the Swedish Heart-Lung Foundation, and Karolinska Institutet. Clint L. Miller has received unrelated project support from AstraZeneca, while no other authors have disclosed potential conflicts of interest.
