Muscle LIM Protein Force-Sensing Mediates Sarcomeric Biomechanical Signaling in Human Familial Hypertrophic Cardiomyopathy.
Muhammad RiazJinkyu ParkLorenzo R SewananYongming RenJonas SchwanSubhash K DasPawel T PomianowskiYan HuangMatthew W EllisJiesi LuoJuli LiuLoujin SongI-Ping ChenCaihong QiuMasayuki YazawaGeorge TellidesJohn HwaLawrence H YoungLei YangCharles C MarboeDaniel L JacobyLorenzo R SewananYibing QyangPublished in: Circulation (2022)
Our studies have uncovered a novel biomechanical mechanism through which dysregulated sarcomeric force production is sensed and leads to pathological signaling, remodeling, and hypertrophic responses. Together, these establish the foundation for developing innovative mechanism-based treatments for HCM that stabilize the Z-disc MLP-mechanosensory complex.