25 February 2016

Hypertrophy of the heart was associated with long non-coding RNA

Oleg Lischuk, N+1

hypercardia.jpg
Cross section of the heart with left ventricular hypertrophy (Wikimedia Commons)

An international team of researchers has found that the development of cardiac hypertrophy under stress is controlled by a previously unknown long non-coding RNA (dncRNA). The results of their work are published in Science Translational Medicine (Viereck et al., Long noncoding RNA Chast promotes cardiac remodeling).

Scientists from Germany, the Netherlands and the UK conducted an analysis on a dncRNA chip isolated from the hearts of mice with transverse aortic stenosis (a model of cardiac hypertrophy developed as a result of pressure overload). During the analysis, they identified a dncRNA molecule, the expression of which is much greater in mice with aortic stenosis than in healthy ones. This molecule was named Chast (cardiac hypertrophy–associated transcript; transcript associated with cardiac hypertrophy).

Further experiments showed that an increase in the expression of Chast leads to the development of hypertrophy of cardiomyocytes (heart muscle cells) in culture and in the mouse heart. Switching off the gene of this dncRNA with an antisense oligonucleotide prevented the development of hypertrophy or eliminated an already developed one.

The researchers also found that the expression of the human Chast homologue was significantly increased in the biopsy of hypertrophied myocardium of patients with aortic stenosis and in cardiomyocytes obtained from embryonic stem cells and subjected to hypertrophic stimulation.

The study of the mechanism of such action of dncRNA showed that it causes hypertrophy of the heart, preventing autophagy (self-destruction) of cardiomyocytes. According to scientists, Chast may become a target for new drugs that prevent myocardial remodeling under conditions of increased stress.

Myocardial hypertrophy is an overgrowth of the heart muscle in response to increased stress. Since the hypertrophied heart is less well supplied with blood and has a smaller volume of chambers compared to a healthy one, patients with hypertrophy develop progressive heart failure.

Long non–coding RNA is a representative of numerous non-coding RNAs that do not directly participate in protein synthesis on the DNA matrix, but perform important regulatory functions.

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