A cardiovascular research team from Beth Israel Deaconess Medical Center (BIDMC) and Brigham and Women's Hospital (BWH), led by BIDMC Principal Investigator Saumya Das, MD, PhD, has been awarded a $4 million Common Fund grant from the National Institutes of Health (NIH) as part of a newly formed program on Extracellular RNA Communication. The five-year grant will focus on identifying microRNA biomarkers in heart disease.
Each year, complications from heart attacks (myocardial infarctions) contribute to more than half a million cases of heart failure and 300,000 cases of sudden cardiac arrest, when the heart suddenly stops. Both of these conditions are closely related to a process known as remodeling, in which the structure and function of the heart changes - or remodels -- following a heart attack.
"Our goal is to explore the role that microRNAs play in predicting which heart-attack patients will go on to experience complications," explains Das, an electrophysiologist in BIDMC's Cardiovascular Institute and co-director of the cardiovascular genetics program within the Outpatient Cardiovascular Clinic.
"Current strategies used to identify the highest risk patients have often been inaccurate," he adds. "We think that a blood test that makes use of microRNA biomarkers could replace existing strategies and more accurately predict which patients might experience poor outcomes and thereby identify who would most benefit from frequent monitoring and medical care." Other investigators who are part of the NIH grant, "Plasma miRNA Predictors of Adverse Mechanical and Electrical Remodeling After Myocardial Infarction," include BIDMC Director of Cardiovascular Research Anthony Rosenzweig, MD, and BWH investigators Raymond Y. Kwong, MD, MPH, and Mark Sabatine, MD, MPH.
microRNAs are one type of extracellular RNA. Once considered nothing more than genomic "junk," microRNAs have more recently been recognized as playing a key role in cellular functions. Several years ago, scientists began to recognize that these small, noncoding RNAs were not only found inside cells, but could also be found in blood and other tissue fluids.
Using patient plasma samples from extensively characterized patients who have suffered heart attacks, the scientific team will first identify which specific microRNAs are related to poor heart remodeling. They will then use cell culture and animal models of heart disease to further prioritize which microRNAs play a functional role in disease progression. Finally, the investigators will validate these prioritized microRNAs as prognostic markers for poor health outcomes after heart attacks in a large prospective clinical trial.
"Ultimately, we think that miRNA-based tests could replace current tests to predict which patients might be at risk of complications and, therefore, be good candidates to receive an implanted defibrillator," says Das. "At the same time, we hope to be able to better predict which individuals are at less risk of complications - and thereby spare them unnecessary and costly procedures."
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