Abstract
Cardiomyopathy Mutations in the gene LMNA , which encodes nuclear envelope proteins, can cause dilated cardiomyopathy associated with arrhythmia and sudden cardiac death. To understand the mechanisms contributing to this disease, Sayed et al. studied induced pluripotent stem cell–derived endothelial cells (iPSC-ECs) from a family harboring an LMNA mutation. They found down-regulation of a protein involved in mechanotransduction, which caused endothelial dysfunction. Lovastatin could induce this protein in iPSC-ECs, improving cardiomyocyte function in coculture and clinical endothelial cell function in two patients treated with the drug. This study demonstrates a workflow for identifying and validating potential drug treatments for patients with cardiolaminopathy. Sci. Transl. Med. 12 , eaax9276 (2020).
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