Featured Research

from universities, journals, and other organizations

Key heart failure culprit discovered in tiny piece of RNA

Date:
March 12, 2014
Source:
Mount Sinai Medical Center
Summary:
A small, but powerful, new player in the onset and progression of heart failure has been discovered by cardiovascular researchers. The researchers have also shown how they successfully blocked the newly discovered culprit to halt the debilitating and chronic life-threatening condition in its tracks.

Medical research (stock image). 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.
Credit: © DragonImages / Fotolia

A team of cardiovascular researchers from the Cardiovascular Research Center at Icahn School of Medicine at Mount Sinai, Sanford-Burnham Medical Research Institute, and 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 12, also show how they successfully blocked the newly discovered culprit to halt the debilitating and chronic life-threatening condition in its tracks.

In the study, investigators identified a tiny piece of RNA called miR-25 that blocks a gene known as SERCA2a, which regulates the flow of calcium within 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.

"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," says study co-senior author Mark Mercola, PhD, professor in the Development, Aging, and Regeneration Program at Sanford-Burnham and professor of Bioengineering at UC San Diego Jacobs School of Engineering. "The results of this study validate our approach to identifying microRNAs as potential therapeutic targets with significant clinical value."

Dr. 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, PhD, 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," says co-lead study author Dongtak Jeong, PhD, 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, MD.

Nearly 6 million Americans suffer from heart failure, which is when the heart becomes weak and cannot pump enough blood and oxygen throughout the body. Heart failure is a leading cause of hospitalization in the elderly. Often, a variety of medications are used to provide heart failure patients temporary relief of their debilitating symptoms. However, these medications do not improve cardiac function or halt the progression of the disease.

"Currently, heart failure medications do not effectively address the underlying mechanisms that weaken contractile function and lead to the enlargement of heart muscle cells," says co-senior study author Roger J. Hajjar, MD, Director of the Cardiovascular Research Center and the Arthur & Janet C. Ross Professor of Medicine at Icahn School of Medicine at Mount Sinai. "Our study provides us with the key evidence we need to begin developing miR-25 as an important new therapeutic target, while adding our successful technique to block this microRNA to our growing arsenal of promising heart failure therapies that we will further develop and test in future clinical trials."

Currently, Dr. Hajjar's laboratory is developing novel gene therapies for patients with heart failure. One therapy, currently in phase IIb/III human clinical trials, uses a modified viral vector to deliver a gene that produces SERCA2a, an enzyme found in healthy heart muscle cells. Another therapy, in preclinical development, uses a disabled virus to deliver a gene called SUMO-1, which shrinks enlarged heart muscle cells and improves cardiac function.


Story Source:

The above story is based on materials provided by Mount Sinai Medical Center. Note: Materials may be edited for content and length.


Journal Reference:

  1. Inhibition of Mir- Improves Cardiac Contractility in the Failing Heart Christine Wahlquist, Dongtak Jeong, Agustin Rojas-Muñoz, Changwon Kho, Ahyoung Lee, Shinichi Mitsuyama, Alain Van Mil, Woo Jin Park, Joost P. G. Sluijter, Pieter A. F. Doevendans, Roger J. Hajjar & Mark Mercola. Inhibition of miR-25 improves cardiac contractility in the failing heart. Nature, March 2014 DOI: 10.1038/nature13073

Cite This Page:

Mount Sinai Medical Center. "Key heart failure culprit discovered in tiny piece of RNA." ScienceDaily. ScienceDaily, 12 March 2014. <www.sciencedaily.com/releases/2014/03/140312150101.htm>.
Mount Sinai Medical Center. (2014, March 12). Key heart failure culprit discovered in tiny piece of RNA. ScienceDaily. Retrieved July 24, 2014 from www.sciencedaily.com/releases/2014/03/140312150101.htm
Mount Sinai Medical Center. "Key heart failure culprit discovered in tiny piece of RNA." ScienceDaily. www.sciencedaily.com/releases/2014/03/140312150101.htm (accessed July 24, 2014).

Share This




More Health & Medicine News

Thursday, July 24, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Condemned Man's US Execution Takes Nearly Two Hours

Condemned Man's US Execution Takes Nearly Two Hours

AFP (July 24, 2014) — America's death penalty debate raged Thursday after it took nearly two hours for Arizona to execute a prisoner who lost a Supreme Court battle challenging the experimental lethal drug cocktail. Duration: 00:55 Video provided by AFP
Powered by NewsLook.com
China's Ageing Millions Look Forward to Bleak Future

China's Ageing Millions Look Forward to Bleak Future

AFP (July 24, 2014) — China's elderly population is expanding so quickly that children struggle to look after them, pushing them to do something unexpected in Chinese society- move their parents into a nursing home. Duration: 02:07 Video provided by AFP
Powered by NewsLook.com
Hundreds in Virginia Turn out for a Free Clinic to Manage Health

Hundreds in Virginia Turn out for a Free Clinic to Manage Health

AFP (July 24, 2014) — America may be the world’s richest country, but in terms of healthcare, the World Health Organisation ranks it 37th - prompting hundreds in Virginia to turn out for a free clinic run by “Remote Area Medical”. Duration 02:40 Video provided by AFP
Powered by NewsLook.com
Idaho Boy Helps Brother With Disabilities Complete Triathlon

Idaho Boy Helps Brother With Disabilities Complete Triathlon

Newsy (July 23, 2014) — An 8-year-old boy helped his younger brother, who has a rare genetic condition that's confined him to a wheelchair, finish a triathlon. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
 
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:  

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:  

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile iPhone Android Web
Follow Facebook Twitter Google+
Subscribe RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins