Illustration of red blood cells moving through clogged Artery to indicate atherosclerosis and need for statin use
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Researchers have genetically sequenced carotid plaque tissue from patients within days after a stroke to determine what might be the biological trigger of such an event. The team, from Tulane University and Ochsner Health, found that samples from recent stroke victims contained messenger RNA that can cause inflammation and processes that degrade a key portion of the plaque.

“The genes identified in our study could be used as targets to develop new drugs or diagnostics to help prevent strokes and heart attacks,” said study senior author Cooper Woods, PhD, associate professor of physiology and medicine at Tulane University School of Medicine

Their results were recently published in Scientific Reports. The study was co-authored by Hernan Bazan, the John Ochsner Endowed Professor for Cardiovascular Innovation at Ochsner Health.

Heart attacks and strokes are a leading cause of death, affecting almost 800,000 people in the US alone each year.  But scientists are still working to understand the primary triggers of this condition. Both ischemic stroke and myocardial infarction are caused when atherosclerotic plaque ruptures. However, a lingering question has been “What causes plaque in arteries to become unstable, leading it to suddenly burst or break away?”

A key obstacle is that researchers haven’t been able to study plaques during a stroke.

In this study, ribosome-depleted total RNA was sequenced from carotid plaques obtained from patients undergoing carotid endarterectomy with high-grade stenosis and who either had a carotid-related ischemic cerebrovascular event within the previous 5 days or had not (i.e. controls).

The team found that plaque rupture was responsible for the greatest percentage of the variability between samples (23.2%), and recently ruptured plaques were “enriched for transcripts associated with inflammation and extracellular matrix degradation.”

The researchers also found co-expression of transcripts for immunoglobulins and B lymphocyte function, matrix metalloproteinases, and interferon response genes. Further analysis supported “the importance of inflammation and inhibition of proliferation and migration coupled with an increase in apoptosis.”

The researchers were surprised to find that ruptured plaques had increased markers of B-cells, a white blood cell whose role in plaque rupture has not previously been appreciated.

Previous studies have relied on carotid artery samples obtained after the patient’s death or months after the stroke or heart attack. This either limits the information that can be obtained or misses events that occur only at the time of rupture.

Carotid artery blockage is a common cause of some ischemic strokes, which happens when the blood supply to part of the brain is interrupted, preventing brain tissue from getting necessary oxygen and nutrients. Because the mechanisms that lead to some strokes and most heart attacks involve the same plaque rupture events, these findings also have implications for heart disease.

“Inflammation is a known risk factor in atherosclerosis, leading to stroke and heart attacks,” Bazan said. “Carotid and coronary plaques develop a protective cap that, for unclear reasons, thins, making strokes and heart attacks more likely.”

The authors concluded that, “The transcriptome of recently ruptured plaques is enriched with transcripts associated with inflammation and fibrous cap thinning and support further examination of the role of B lymphocytes and interferons in atherosclerotic plaque rupture.”

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