In the Literature.

Abstract

Research indicates that the majority of the noncoding genome is actively transcribed, generating thousands of small and long regulatory noncoding RNAs that play important roles in numerous cell types. Now investigators have provided a specific example of how 1 such regulatory noncoding RNA might be harnessed to improve cardiovascular health. In a Science Translational Medicine article, a team led by scientists at the University of Lausanne Medical School in Switzerland report that a long noncoding RNA (lncRNA) called Wisper is highly abundant in cardiac fibroblasts, the culprits behind fibrotic scar formation, and that depleting the molecule can protect heart function and decrease scarring after myocardial infarction in mice. Experiments in both culture and mouse models of heart injury revealed that Wisper controls various molecules involved in proscarring pathways in cardiac fibroblasts. When the investigators analyzed human tissue, they found a 57% identical lncRNA within the human genome, which they dubbed WISPER. Furthermore, in heart biopsy samples from human patients with aortic stenosis, WISPER levels correlated with fibrosis severity. Also, the lncRNA’s effects on scarring were specific to cardiac cells and not fibroblasts from other tissue types. For example, both the heart and kidney develop severe fibrosis, but Wisper is only induced in the heart. “For the first time, we have identified a therapeutic target that is highly specific to both the heart and fibroblasts within the heart, allowing the direct modulation of cardiac fibrosis with unprecedented specificity,” said coauthor Samir Ounzain, PhD. Additional studies are needed to determine whether cardiac fibroblast-specific lncRNAs such as WISPER may be promising therapeutic targets for cardiac fibrosis and heart failure. Also, because it is possible to detect lncRNAs in human plasma, measuring circulating concentrations of molecules such as WISPER might provide a noninvasive means to monitor certain aspects of cardiovascular health. “Cardiac fibrosis is now emerging as a critical process to tackle therapeutically, and sadly no current therapies exist. Our therapeutic target offers an unprecedented opportunity to tackle this issue in a highly specific manner,” said Dr. Ounzain.