Abnormal muscle mechanosignaling triggers cardiomyopathy in mice with Marfan syndrome.

Patients with Marfan syndrome (MFS), a multisystem disorder caused by mutations in the gene encoding the extracellular matrix (ECM) protein fibrillin 1, are unusually vulnerable to stress-induced cardiac dysfunction. The prevailing view is that MFS-associated cardiac dysfunction is the result of aortic and/or valvular disease. Here, we determined that dilated cardiomyopathy (DCM) in fibrillin 1-deficient mice is a primary manifestation resulting from ECM-induced abnormal mechanosignaling by cardiomyocytes.