Deletion of Sphingosine 1-Phosphate receptor 1 in cardiomyocytes during development leads to abnormal ventricular conduction and fibrosis.

ABSTRACT: Sphingosine 1-Phosphate receptor 1 (S1P₁ , encoded by S1pr1) is a G protein-coupled receptor that signals in multiple cell types including endothelial cells and cardiomyocytes. Cardiomyocyte-specific deletion of S1pr1 during mouse development leads to ventricular noncompaction, with 44% of mutant mice surviving to adulthood. Adult survivors of embryonic cardiomyocyte S1pr1 deletion showed cardiac hypertrabeculation consistent with ventricular noncompaction. Surprisingly, systolic function in mutant mice was preserved through at least 1 year of age. Cardiac conduction was abnormal in cardiomyocyte S1pr1 mutant mice, with prolonged QRS intervals in mutants as compared with littermate control mice. Immunostaining of hearts from S1pr1 mutant embryos displayed a zone of intermediate

SUBMITTER: Jorgensen R 

PROVIDER: S-EPMC8496155 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature