UCLA scientists find molecule that triggers heart disease
Scientists at University of California (UCLA) have identified a molecule that appears to play a key role in the development of heart failure. The scientists found that blocking the molecule, known as chaer, in animal studies prevented the animals from developing heart failure.
Although the research is still at an early stage, future drugs that target chaer or related signalling pathways may hold promise for treating or preventing heart failure, a condition that afflicts about 30 million people in India. The results of the study were published in the journal Nature Medicine.
Chaer is not a protein; it is made of RNA, DNA’s simpler cousin, and belongs to a category of RNA molecules called long non-coding RNA. It’s called “non-coding” because the molecules don’t encode and get translated into proteins, as do other RNAs. Non-coding RNAs have been considered part of the “dark matter” of biology because they are abundant and diverse in cells, and the DNA that encodes these RNAs accounts for most of plant and animal genomes, yet their roles have been largely unexplored.
“The observation that a single IncRNA molecule can activate a broad set of heart-failure related genes was a big surprise,” said Yibin Wang, the study’s senior author and a professor in the departments of anesthesiology, physiology and medicine at the David Geffen School of Medicine at UCLA, while speaking to the University’s news website. “The findings provide us a better understanding of the molecular processes of heart failure, which we hope eventually to target with effective therapies.”
When someone has heart failure, their muscle tissues progressively thicken and stiffen. This reduces the heart’s ability to pump blood to the rest of the body. Current therapies can slow the disease in its early stages but often become less effective as the disease progresses.
When the researchers eliminated chaer in mice that were similarly induced by high blood pressure, they observed that the animals were essentially protected from heart failure, having little of the usual heart overgrowth (hypertrophy), scar-like remodeling of tissue (fibrosis), and loss of cardiac function. The knockout of chaer also blocked the usual heart failure-related pattern of gene activity in the mice’s heart muscle cells. Experiments in human heart cell-based models of heart failure yielded similar results.
Wang and colleagues hope to find molecules that could be turned into chaer-blocking drugs. They also have begun to explore other signalling pathways that need to be present for chaer to produce its heart failure-inducing activity, and are already testing compounds that inhibit those signals.