Innovative Mechanosensing Approach Shows Potential for Treating Heart Fibrosis

Recent research from Stanford Cardiovascular Institute has unveiled a novel strategy to combat cardiovascular fibrosis by targeting the mechanosensing mechanisms of heart cells. Cardiac fibrosis, characterized by the stiffening and scarring of heart tissue, is a major contributor to various heart diseases, leading to impaired heart function and eventual heart failure. Despite its significant impact, effective treatments remain elusive.

The study, published in Nature, introduces a dual approach that not only interferes with the biochemical signals triggering fibroblast activation—the process where cells responsible for scarring are turned on—but also modulates the mechanical cues that sustain the fibrotic environment. This is crucial because once fibroblasts activate and promote tissue stiffening, reversing this process becomes highly challenging.

By analyzing single-cell sequencing data, the researchers identified SRC, a key mechanosensing protein mainly found in fibroblasts within the heart. SRC acts as a cellular switch that senses mechanical stress. In diseased hearts, SRC activity is elevated, perpetuating fibrosis. The team screened thousands of compounds and identified saracatinib, an existing cancer drug, as an effective inhibitor of SRC.

Laboratory experiments demonstrated that the combined inhibition of SRC and the TGFβ pathway—a major driver of fibroblast activation—significantly reduced fibrosis and restored heart tissue flexibility. These effects were observed in cell cultures, engineered heart tissues, and mouse models of heart failure, suggesting promising translational potential.

Lead researcher Dr. Sangkyun Cho emphasized that targeting stromal cell mechanosensing could selectively disrupt the fibrotic cycle without harming other vital heart functions. Senior author Dr. Joseph Wu highlighted that this approach could pave the way for 'mechanotherapies' that aim not just to slow disease progression but to reverse existing damage.

Looking forward, the researchers plan to explore the application of this strategy to other fibrotic conditions affecting lungs, skin, or liver, potentially broadening its therapeutic impact. This breakthrough signals a new era in the treatment of fibrotic diseases, offering hope for millions affected worldwide.