Francesco Ramirez’s group found that abnormal extracellular matrix (ECM) signaling results in dilated cardiomyopathy (DCM) in fibrillin 1–deficient mice. These mice develop enlarged and dysfunctional heart, altered physical properties of myocardial tissue, and biochemical evidence of chronic mechanical stress, including increased angiotensin II type I receptor (AT1R) signaling. Consistent with abnormal mechanosignaling, normal cardiac size and function were restored by treatment with an AT1R antagonist. Therefore, fibrillin 1 is implicated in the physiological adaptation of cardiac muscle to elevated workload. These findings explain why patients with Marfan syndrome are unusually vulnerable to stress-induced cardiac dysfunction.

http://www.jci.org/articles/view/71059

Posted by Nicola Brunetti-Pierri, MD, FACMG