Olmesartan Restores LMNA Function in Haploinsufficient Cardiomyocytes

Document Type

Article

Publication Date

2025

Publication Title

Circulation

Abstract

BACKGROUND: Gene mutations are responsible for a sizeable proportion of cases of heart failure. However, the number of patients with any specific mutation is small. Repositioning of existing US Food and Drug Administration-approved compounds to target specific mutations is a promising approach to efficient identification of new therapies for these patients.

METHODS: The National Institutes of Health Library of Integrated Network-Based Cellular Signatures database was interrogated to identify US Food and Drug Administration-approved compounds that demonstrated the ability to reverse the transcriptional effects of

RESULTS: Several angiotensin receptor blockers were identified from our in silico screen. Of these, olmesartan significantly elevated the expression of sarcomeric genes and rate and force of contraction and ameliorated arrhythmogenic potential. In addition, olmesartan exhibited the ability to reduce phosphorylation of extracellular signal-regulated kinase 1 in

CONCLUSIONS: In silico screening followed by in vitro validation with induced pluripotent stem cell-derived models can be an efficient approach to identifying repositionable therapies for monogenic cardiomyopathies.

Volume

151

Issue

20

First Page

1436

Last Page

1448

Comments

Fredrik Meijer Heart and Vascular Institute

Helen DeVos Children's Hospital

DOI

10.1161/circulationaha.121.058621

ISSN

1524-4539

PubMed ID

40166828

Link to Full Text

Share

COinS