Key Heart Failure Culprit Discovered
A team of cardiovascular researchers from at Icahn School of Medicine at Mount Sinai in NewYork and the University of California, San Diego have identified a small but powerful new player in the onset and progression of heart failure. Their findings, published in the journal Nature on March 12th 2014, also show how they successfully blocked the newly discovered culprit to halt the debilitating and chronic life-threatening condition in its tracks.
A release from Mount Sinai reports that the investigators identified a tiny piece of RNA called miR-25 that blocks a gene known as SERCA2a, which regulates the flow of calcium in and out of heart-muscle cells. Decreased SERCA2a activity is one of the main causes of poor contraction of the heart and enlargement of heart-muscle cells leading to heart failure.
Using a functional screening system developed by researchers at Sanford-Burnham, the research team discovered miR-25 acts pathologically in patients suffering from heart failure, delaying proper calcium uptake in heart-muscle cells.
The release quotes study co-senior author Mark Mercola, Ph.D. as assaying, "Before the availability of high-throughput functional screening, our chance of teasing apart complex biological processes involved in disease progression like heart failure was like finding a needle in a haystack. The results of this study validate our approach to identifying microRNAs as potential therapeutic targets with significant clinical value."
Mercola's laboratory has pioneered the use of robotic high-throughput methods of drug discovery to identify new targets for heart failure. According to co-lead study authors Christine Wahlquist and Agustin Rojas Muñoz, Ph.D., developers of the approach and researchers in Mercola's lab at Sanford-Burnham, they used high-throughput robotics to sift through the entire genome for microRNAs involved in heart-muscle dysfunction.
Subsequently, the researchers at the Cardiovascular Research Center at Icahn School of Medicine at Mount Sinai found that injecting a small piece of RNA to inhibit the effects of miR-25 dramatically halted heart-failure progression in mice. In addition, it also improved their cardiac function and survival.
"In this study, we have not only identified one of the key cellular processes leading to heart failure, but have also demonstrated the therapeutic potential of blocking this process," said co-lead study author Dongtak Jeong, Ph.D., a post-doctoral fellow at the Cardiovascular Research Center at Icahn School of Medicine at Mount Sinai in the laboratory of the study's co-senior author Roger J. Hajjar, M.D.