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Biological Chemistry

Targeting Noncoding RNAs To Treat Heart Disease

Drug Development: Silencing long noncoding RNA prevents harmful thickening of heart muscle in mice

by Michael Torrice
February 26, 2016 | A version of this story appeared in Volume 94, Issue 8

Three mouse heart photos.
Credit: Sci. Transl. Med.
A small RNA that silences Chast can prevent the overgrowth of heart tissue in cardiac hypertrophy. Mice given this inhibitory RNA had smaller hearts (right) than those given a silencing RNA with a scrambled sequence (center).

Not all transcribed RNAs code for proteins. The roles of these noncoding RNAs aren’t fully understood, but some regulate pathways involved in gene expression. A study now reports that one long noncoding RNA called Chast could serve as a drug target for cardiac hypertrophy, a heart disease in which cardiac muscle thickens (Sci. Transl. Med. 2016, DOI: 10.1126/scitranslmed.aaf1475). Stress to the heart, sometimes from a narrowing aorta, causes this harmful overgrowth of tissue, which impairs the organ’s function and eventually leads to heart failure. Thomas Thum of Hannover Medical School and colleagues identified Chast by inducing cardiac hypertrophy in mice and looking for noncoding RNA transcripts with increased expression levels in cardiac muscle cells. Also, the scientists found elevated levels of a human homolog of Chast in patients with a heart condition that leads to cardiac hypertrophy.The team showed that targeting Chast in mice could affect disease progression. They prevented the thickening of heart muscle after inducing hypertrophy by giving the mice a small RNA that inhibits Chast. This silencing RNA also shrank enlarged hearts of mice already affected by the disease.


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