Blocking RNA MALAT1 Reduces Heart Abnormality in Pulmonary Hypertension, Study Shows

Eliminating a long noncoding RNA reduced heart-muscle enlargement in mice with pulmonary hypertension (PH), according to a study.

The RNA, known as MALAT1, balances the turnover — or production, growth and death — of smooth muscle cells lining blood vessels. MALAT1 stands for metastasis-associated lung adenocarcinoma transcript 1.

The study, “Analysis of hypoxia-induced noncoding RNAs reveals metastasis-associated lung adenocarcinoma transcript 1 as an important regulator of vascular smooth muscle cell proliferation,” was published in the journal Experimental Biology and Medicine.

Dr. Matthias Brock of the University Hospital of Zurich’s Division of Pulmonology led the research. The hospital is part of the University of Zurich.

PH is caused by high blood pressure in the blood vessels of the lungs. If left untreated, it can lead to heart abnormalities and failure.

Changes in the lungs’ blood vessels, which scientists call vascular remodeling, are a hallmark of PH. When people have the disease, their endothelial cells — which line the blood vessels — and their smooth muscle cells grow, die, and travel in the body abnormally.

The pathways leading to the changes are not well understood. Knowing more about them will help scientists find new targets for therapies.

MALAT1 regulates the activity of some genes. It controls the normal turnover of smooth muscle cells in blood vessels by balancing their multiplication and death.

Researchers discovered that, in a laboratory environment, MALAT1 is more active and its levels higher in cells grown in an oxygen-reduced, or hypoxia, environment. Eliminating MALAT1 significantly decreased the proliferation and migration of pulmonary artery smooth muscle cells.

The team also found a much higher level of MALAT1 in the lungs of an oxygen-reduced mouse model of PH, which they said impaired the functioning of the right heart. A therapy targeting MALAT1 improved the heart-enlargement issue.

This study “provides novel insights in the pathogenesis of pulmonary vascular remodelling and confirms that lncRNAs [long noncoding RNAs, in this case, MALAT1] affect the expression of important cell cycle regulators that favour the pro-proliferative phenotype of vascular smooth muscle cells,” Brock said in a press release.

Dr. Steven R. Goodman, editor in chief of the journal Experimental Biology and Medicine, said “Brock and colleagues provide the seminal study of the functional role of MALAT1 in the pulmonary vasculature. They demonstrate that MALAT1 is a potential target for reducing heart hypertrophy during hypoxia-induced pulmonary hypertension.”