Micro Molecules Contribute Mightily To Heart Problem

Their findings, available online this week and in an upcoming issue of the Proceedings of the National Academy of Sciences, are part of a fast-growing research field revealing the wide importance of so-called micro ribonucleic acids, or miRNAs, in numerous bodily functions, including cancer, cell death and cell growth.

"They haven't been studied for very long," said Dr. Eric Olson, chairman of molecular biology and senior author of the study. "These particular micro RNAs aren't just markers of heart failure. They're actually able to cause the disease, at least in mice.

"This is the first evidence for the involvement of micro RNAs in adult heart disease," said Dr. Olson, who directs the Nancy B. and Jake L. Hamon Center for Basic Research in Cancer and the Nearburg Family Center for Basic Research in Pediatric Oncology.

Eventually, manipulating micro RNAs might be a way to treat heart disease, the researchers reported. A micro RNA can be blocked with a short complementary fragment of genetic material engineered to attach to RNA and neutralize it.

The process of identifying the damage-causing micro RNAs started with the researchers investigating whether any micro RNAs were present at abnormal levels in diseased, enlarged hearts of mice. Sixteen of the 28 such micro RNAs identified were focused on because they were similar to those found in humans and rats. The researchers found that some of the same micro RNAs are present at abnormal concentrations in diseased human hearts, suggesting that these micro RNAs also play a role in human heart disease.

Dr. Olson's team eventually zeroed in on one micro RNA, called miR-195, which had both visible and functional effects on the heart. These effects were established by creating genetically modified mice that had higher-than-normal amounts of miR-195. Those mice had misshapen hearts and decreased pumping power.

In addition, adding miR-195 to heart cells cultured in dishes made the cells larger and more disorganized.

Because some of the micro RNAs studied are known to be involved in other cell processes, the researchers speculate that these particular RNAs play a role in cell division or growth of heart muscle cells. Further research is needed to determine the mechanism by which miR-195 causes the heart to enlarge, Dr. Olson said.

Other UT Southwestern researchers involved in the study were Dr. Eva van Rooij, postdoctoral researcher in molecular biology and the study's lead author; Lillian Sutherland, research scientist in molecular biology; Dr. Ning Liu, postdoctoral researcher in molecular biology; graduate student research assistant Andrew Williams; research technician John McAnally; Dr. Robert Gerard, associate professor of internal medicine and molecular biology; and Dr. James Richardson, professor of pathology and molecular biology.

The work was supported by the National Institutes of Health, the Donald W. Reynolds Cardiovascular Clinical Research Center at UT Southwestern and the Welch Foundation.