�The developing and touch on of heart tissue and blood vessels is intimately tied to a tiny piece of ribonucleic acid (RNA) that is launch nowhere else in the body, researchers at UT Southwestern Medical Center have found.
Because of its specificity to the cardiovascular system, this "microRNA" is an attractive potentiality target for therapeutic treatment, the researchers said.
"Manipulating this microRNA provides a totally new way of addressing cardiovascular disorders," said Dr. Eric Olson, chairman of molecular biology and senior author of a work appearing in today's issue of
MicroRNAs are midget snippets of genetic material, naturally produced by the body, that help tweak the production of proteins by DNA. More than 500 have already been identified.
In the current work, the researchers focused on a specific microRNA called miR-126, which was already known to be associated with blood vessels. They found that miR-126 is found exclusively in a class of cells called endothelial cells, which line the inside surfaces of blood vessels.
Endothelial cells control the development of new blood vessels in developing embryos; the repair of injured origin vessels; and the creation of blood vessels to support development tumors.
The researchers genetically engineered mice to lack miR-126, and found that about 40 percent of them died before or just after parentage. These mice showed cardiovascular abnormalities such as fragile, leaking lineage vessels.
The surviving mice, however, appeared normal and lived to adulthood. The researchers complete that miR-126 is important in creating new vessels, but one time the cardiovascular system is established, it is not needed to maintain the system.
However, the surviving mice were less able to recover from a simulated heart attack. Almost all mice wanting miR-126 died within threesome weeks, while 70 percentage of normal mice survived for at least three weeks.
The researchers also tried and true the role of miR-126 in the branching of blood vessels using cut sections of mouse aortas in acculturation. When civilized with outgrowth factors that stimulate ramous, aortal sections from normal mice displayed branching of their endothelial cells.
Aortal sections from mice lacking miR-126, however, showed much less branching.
"MicroRNA research represents a new frontier in sympathy and treating human disease. This is just a hint of what can come," aforementioned Dr. Olson, director of the Nancy B. and Jake L. Hamon Center for Basic Research in Cancer and the Nearburg Family Center for Basic Research in Pediatric Oncology.
The researchers have filed various patents related to miR-126, and design to licence it for development as a curative agent through Miragen Therapeutics, a Boulder-based company co-founded by Dr. Olson, which UT Southwestern owns fairness in.
Other UT Southwestern researchers involved in the study were lead writer Dr. Shusheng Wang, post doc researcher in molecular biology; Dr. Arin Aurora, post doc researcher in molecular biology; graduate educatee Brett Johnson; Xiaoxia Qi, research scientist in molecular biology; John McAnally, research associate in molecular biology; Dr. Joseph Hill, prof of interior medicine; Dr. James Richardson, professor of pathology; and Dr. Rhonda Bassel-Duby, prof of molecular biology.
The work was supported by the National Institutes of Health, the Donald W. Reynolds Clinical Cardiovascular Research Center, the Sandler Foundation for Asthma Research, the Welch Foundation and the American Heart Association.
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Dr. Eric Olson -- witness here.
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