Final Report Summary - CALMIRS (RNA-based regulation of signal transduction – Regulation of calcineurin/NFAT signaling by microRNA-based mechanisms)
In ERC CALMIRS, we demonstrated that intracellular signaling cascades in the diseased heart activate a new class of very small genes that do not code for proteins but have a strong regulatory function. For example, we discovered that these “mini-genes” determine if a heart muscle becomes very thick or rather very thin; they also regulate how many of the smallest of blood vessels are present in the heart; fine-tune the activation of other signaling cascades; and determine how long proteins in the heart muscle exist or are degraded. Quite remarkably, the products of this new class of “mini-genes” are even secreted by diseased hearts in tiny vesicles that allow communication between heart muscle cells and cells that line blood vessels, and are even detectable in the bloodstream of heart failure patients, where they can be picked up as new diagnostic tools. Finally, we developed technology to therapeutically block or stimulate these “mini-genes”, resulting in delay or even prevention of the development of heart disease.