Yale Researchers Identify RNA That Controls Cholesterol

Researchers found that miR-148a alters LDL receptors in liver cells, affecting the regulation of HDL cholesterol levels in both mice and humans.

A new study from Yale University reveals that miR-148a modifies LDL receptors in liver cells of both mice and humans and suppresses a gene that is critical for controlling levels of HDL cholesterol.

High levels of LDL cholesterol — the “bad” cholesterol — increase the risk of heart disease, the leading cause of death in the United States. A Yale-led research team has identified an RNA molecule that plays an important role in regulating cholesterol. Therapeutic targeting of this non-coding RNA markedly reduces LDL while boosting HDL, the good cholesterol.

The finding, published online ahead of print in Nature Medicine, may lead to new therapies designed to decrease high cholesterol and heart disease.

The researchers used a high-throughput screening technique to identify which tiny RNA molecules, or microRNAs, influence LDL cholesterol levels in the blood. They found that a particular RNA, known as miR-148a, modifies LDL receptors in liver cells of both mice and humans. They also discovered that miR-148a suppresses a gene that is critical for controlling levels of HDL cholesterol.

“The key finding is the identification of another molecular target that could be used for treating high levels of bad cholesterol, and potentially treating cardiovascular disease,” said Carlos Fernandez-Hernando, associate professor of comparative medicine and pathology, and the study’s senior author. “By blocking this microRNA pharmacologically, we can reduce bad cholesterol.”

“Our work also establishes miR-148a as a promising therapeutic target to increase levels of good cholesterol,” noted Leigh Goedeke, a post-doctoral associate at Yale and lead author of the study. “We may have found a new treatment option to simultaneously reduce two risk factors of heart disease.”

Reference: “MicroRNA-148a regulates LDL receptor and ABCA1 expression to control circulating lipoprotein levels” by Leigh Goedeke, Noemi Rotllan, Alberto Canfrán-Duque, Juan F Aranda, Cristina M Ramírez, Elisa Araldi, Chin-Sheng Lin, Norma N Anderson, Alexandre Wagschal, Rafael de Cabo, Jay D Horton, Miguel A Lasunción, Anders M Näär, Yajaira Suárez and Carlos Fernández-Hernando, 5 October 2015, Nature Medicine.
DOI: 10.1038/nm.3949