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Statin therapy improves endothelial dysfunction

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The molecular mechanisms underlying LMNA-related dilated cardiomyopathy (DCM) remain poorly understood. Sayed et al. now report that iPSC–derived endothelial cells (ECs) generated from a family with LMNA-related DCM exhibit decreased functionality. Transcriptional profiling of the LMNA mutant iPSC-ECs implicated the transcription factor KLF2 as an important regulator of EC dysfunction. Lovastatin induced KLF2 and improved endothelial dysfunction in LMNA iPSC-ECs and in patients with LMNA-related DCM. Furthermore, lovastatin improved the functional phenotype of LMNA iPSC-cardiomyocytes when cocultured with LMNA iPSC-ECs.

Nature Reviews Drug Discovery 19, 588 (2020)

References

  1. 1.

    Sayed, N. et al. Clinical trial in a dish using iPSCs shows lovastatin improves endothelial dysfunction and cellular cross-talk in LMNA cardiomyopathy. Sci. Transl Med. 12, eaax9276 (2020)

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