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Intermountain Team Reports on miRNAs as Biomarkers of Imminent Heart Attack


By Doug Macron

Researchers from the Intermountain Medical Center Heart Institute this week reported the results of a small pilot study showing that a set of three blood-borne microRNAs could serve as biomarkers for an imminent heart attack.

Though preliminary, the findings suggest that the small, non-coding RNAs might be used to identify patients at very high risk for heart attacks so that they can receive preventative treatment, Jeffrey Anderson, the study's senior author and chief of cardiovascular research at Intermountain, said.

The findings were presented this week at the American College of Cardiology's 61st Annual Scientific Session.

"About half of all heart attacks occur in patients with no previous signs of heart disease,” Anderson said in a statement. “The heart attack is a surprise, and very often it's deadly.”

Currently, physicians use a set of guidelines to determine a patient's risk for a heart attack including age, sex, cholesterol and blood pressure levels, and family history, he noted. Yet these have poor predictive value and only offer a risk profile over a ten-year period.

“There is a need for better markers,” Anderson told Gene Silencing News.

Familiar with the growing body of literature showing a role for miRNAs in the heart, Anderson and his team focused their efforts on a series of miRNAs that have previously been associated with cardiovascular disease: miR-122, -145, -375, -134, -499, and -9.

“We thought to start with those and see what we get in the specific setting of trying to predict an imminent heart attack,” Anderson said.

According to the poster presented at the ACC meeting, certain miRNAs have been found to be dysregulated shortly after heart attack, but are unaffected in experimental models of the condition. “Therefore, they might represent independent predictions of incident [myocardial infarction] risk.”

Anderson and his colleagues tapped Intermountain's extensive databank of cardiovascular DNA and blood specimens, and collected plasma samples from 85 patients sorted into four groups: those who provided blood seven days before a heart attack; those who provided blood 36 hours after a heart attack; patients with cardiac disease but who had not had a heart attack either a year before or a year after blood sample collection; and healthy patients.

RNA was extracted from the samples, and the candidate miRNAs were profiled using Life Technologies' TaqMan microRNA assays.

“Relative [miRNA] expression … was evaluated using the comparative Ct method, with miR-16 as an endogenous control for data normalization,” according to the poster. “Group comparisons were performed using linear least squares regression.”

After adjusting for age and gender associations, the investigators found that three miRNAs — miR-122, -145, and -375 — were “significantly down-regulated in the pre-heart attack group versus the non-heart attack patients, it adds.

Additionally, miR-122 was found to be significantly down-regulated in patients who gave blood after their heart attacks compared with those who had never had a heart attack or had not experienced one within a year of blood sample collection.

“No significant differences in microRNA expression between healthy controls and non-MI patients were observed,” the poster concludes.

The results of the study are currently being prepared for submission to a peer-reviewed publication.

Anderson conceded that the study was small, in part due to the difficulty in finding blood samples taken from patients just days before a heart attack. However, he is hoping to conduct a prospective, multi-center study in a larger patient population.

hould the findings of that effort prove positive, Anderson ultimately sees the development of a point-of-care device that can run an miRNA analysis using a small amount of blood.

He noted that selection of the right patient population for the study would likely help with compliance, a significant hurdle given the need for frequent blood samples.

“Diabetics are one very high-risk group, for example, and we might start with them,” Anderson noted. “They are used to getting finger sticks multiple times a day, so if you could complex whatever machine they have that is doing glucose analysis with something that's measuring these microRNAs, that might be one group to start with.”

He added that diabetics would also be a logical group to begin working with clinically since diabetes is “probably the strongest of all” risk factors for heart attack.

“It increases the risk three to five fold,” Anderson explained. “In fact, it's considered to be a coronary risk equivalent. In other words, the risk of somebody with diabetes having a heart attack is as high as somebody who has already had a heart attack having a second one.”

Have topics you'd like to see covered in Gene Silencing News? Contact the editor
at dmacron [at] genomeweb [.] com

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