Navigation Links
Genome regions once mislabeled 'junk' linked to heart failure

Large sections of the genome that were once referred to as "junk" DNA have been linked to human heart failure, according to research from Washington University School of Medicine in St. Louis.

So-called junk DNA was long thought to have no important role in heredity or disease because it doesn't code for proteins. But emerging research in recent years has revealed that many of these sections of the genome produce RNA molecules that, despite not being proteins, still have important functions in the body. RNA is a close chemical cousin to DNA.

Molecules now associated with these sections of the genome are called noncoding RNAs. They come in a variety of forms, some more widely studied than others. Of these, about 90 percent are called long noncoding RNAs, and exploration of their roles in health and disease is just beginning.

In a recent issue of the journal Circulation, Washington University investigators report results from the first comprehensive analysis of all RNA molecules expressed in the human heart. The researchers studied nonfailing hearts and failing hearts before and after patients received pump support from left ventricular assist devices (LVAD). The LVADs increased each heart's pumping capacity while patients waited for heart transplants.

"We took an unbiased approach to investigating which types of RNA might be linked to heart failure," said senior author Jeanne M. Nerbonne, PhD, the Alumni Endowed Professor of Molecular Biology and Pharmacology. "We were surprised to find that long noncoding RNAs stood out. In fact, the field is evolving so rapidly that when we did a slightly earlier, similar investigation in mice, we didn't even think to include long noncoding RNAs in the analysis."

Heart failure refers to a gradual loss of heart function. The left ventricle, the heart's main pumping chamber, becomes less efficient. Blood flow diminishes, and the body no longer receives the oxygen needed to go about daily tasks. Sometimes the condition develops after an obvious trigger such as a heart attack or infection, but other times the causes are less clear.

In the new study, the investigators found that unlike other RNA molecules, expression patterns of long noncoding RNAs could distinguish between two major types of heart failure and between failing hearts before and after they received LVAD support.

"We don't know whether these changes in long noncoding RNAs are a cause or an effect of heart failure," Nerbonne said. "But it seems likely they play some role in coordinating the regulation of multiple genes involved in heart function."

Nerbonne pointed out that all types of RNA molecules they examined could make the obvious distinction: telling the difference between failing and nonfailing hearts. But only expression of the long noncoding RNAs was measurably different between heart failure associated with a heart attack (ischemic) and heart failure without the obvious trigger of blocked arteries (nonischemic). Similarly, only long noncoding RNAs significantly changed expression patterns after implantation of left ventricular assist devices.

Because of the difficulty in obtaining human heart tissue, the study's sample size was relatively small, Nerbonne said. Her team analyzed eight nonfailing hearts, eight hearts in ischemic heart failure and eight hearts in nonischemic heart failure. Though small, the study is unique because each of the 16 failing hearts was sampled twice, once before and once after LVAD support.

According to Nerbonne, this before-and-after sampling of heart tissue is an unusual feature of this study and one of its strengths. Cardiac surgeons first removed a sample of heart tissue while implanting the LVAD. Then, months later, transplant surgeons sampled the same failing hearts when each patient received a new donor organ. Previous studies comparing heart function before and after implanting a pump used samples taken from different patients.

This double sampling of the same organ is important for understanding what is happening on a molecular level to failing heart tissue when a pump literally takes some of the load off.

"It's clear that some patients experience a change in the structure and physiology of the heart tissue following pump support, and in some patients that change results in improved heart function," Nerbonne said. "One interesting question is whether these long noncoding RNAs could be a measure of whether the failing heart is getting better with an LVAD."

Indeed, using the nonfailing heart samples for comparison, about 10 percent of the long noncoding RNA expression that was disturbed in the failing hearts improved or returned to normal following LVAD support. While 10 percent may seem modest, only about 3 percent, at best, of other types of RNA expression returned to normal after pump support.

Nerbonne also is interested in exploring whether measures of long noncoding RNAs could be an early predictor of the disease, ideally before symptoms of heart failure even develop.

Nerbonne pointed out that this study was made possible by a number of important resources, including recent advances in genome sequencing and the availability of tissues through the Washington University Translational Cardiovascular Biobank & Repository (TCBR).

Continuing to plumb these largely unexplored parts of the genome, Nerbonne and her colleagues plan to continue to work closely with the TCBR to facilitate studies of long noncoding RNAs in other cardiac conditions. Specifically, they are interested in atrial fibrillation, the most common irregular heart rhythm, and in comparing adult versus pediatric heart failure, an analysis that may illuminate the role of noncoding RNA in the heart's early development.


Contact: Diane Duke Williams
Washington University School of Medicine

Related medicine news :

1. Researchers at LSTM part of the international team to sequence the tsetse genome
2. How well did you sequence that genome? NIST, consortium partners have answer
3. Whole genome analysis, stat
4. Viewpoint addresses IOM report on genome-based therapeutics and companion diagnostics
5. Drug discovery potential of natural microbial genomes
6. CytoGenX Corp. Announces the Release of Assure™ Whole-Genome Microarray
7. Malignant cells adopt a different pathway for genome duplication
8. Burmese python genome reveals extreme adaptation
9. A CNIO study recreates the history of life through the genome
10. The National Cancer Institute is Presenting “Acquisition of High Quality Tissues to Support Genome Studies” at Sample Prep East in Cambridge, MA, December 9-10, 2013
11. Worlds first IVF baby born after preimplantation genome sequencing is now 11 months old
Post Your Comments:
Related Image:
Genome regions once mislabeled 'junk' linked to heart failure
(Date:11/27/2015)... CA (PRWEB) , ... November 27, 2015 , ... According ... at the recent 2015 American Dental Association meeting in Washington D.C. revolved around the ... protect a patient’s overall health. The talk stressed the link between periodontal disease (more ...
(Date:11/27/2015)... ... November 27, 2015 , ... The ... in America. As people age, more care is needed, especially with Alzheimer’s, dementia ... medical professionals are being overworked. The forgotten part of this equation: 80 percent ...
(Date:11/27/2015)... ... November 27, 2015 , ... "When I was traveling, ... from Hillside, N.J. "Many people catch diseases simply from sitting on such dirty ... be protected from germs." , He developed the patent-pending QUDRATECS to eliminate the ...
(Date:11/27/2015)... ... 27, 2015 , ... ProSidebar: Fashion is a set of 30 ... ProSidebar: Fasion, video editors can easily add an informative sidebar to any FCPX production. ... Utilize presets featuring self-animating drop zones, lines, bars, and text with the ease of ...
(Date:11/27/2015)... ... November 27, 2015 , ... Intellitec ... Dynamics SL User Group (MSDSLUG). Recognized as Microsoft’s official group for end users ... Dynamics SL software users, partners, industry experts and representatives. Intellitec Solutions’ membership status ...
Breaking Medicine News(10 mins):
(Date:11/26/2015)... , Nov. 26, 2015 Research ... addition of the "2016 Future Horizons and ... (TDM) Market: Supplier Shares, Country Segment Forecasts, Competitive ... --> --> ... analysis of the Italian therapeutic drug monitoring market, ...
(Date:11/25/2015)... 25, 2015 ... the "Global Brain Monitoring Devices Market ... --> ) has announced the ... Devices Market 2015-2019" report to their ... ( ) has announced the addition ...
(Date:11/25/2015)... 25, 2015  The American Academy of Pediatrics ... and the March of Dimes cheered today,s signature ... Infants Act of 2015 (S.799), which takes ... born exposed to drugs, such as opioids, and ... all three organizations have worked together leading advocacy ...
Breaking Medicine Technology: