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  • Retinoic acid signaling is directly activated in cardiomyocytes and protects mouse hearts from apoptosis after myocardial infarction.

Retinoic acid signaling is directly activated in cardiomyocytes and protects mouse hearts from apoptosis after myocardial infarction.

eLife (2021-10-09)
Fabio Da Silva, Fariba Jian Motamedi, Lahiru Chamara Weerasinghe Arachchige, Amelie Tison, Stephen T Bradford, Jonathan Lefebvre, Pascal Dolle, Norbert B Ghyselinck, Kay D Wagner, Andreas Schedl
ABSTRACT

Retinoic acid (RA) is an essential signaling molecule for cardiac development and plays a protective role in the heart after myocardial infarction (MI). In both cases, the effect of RA signaling on cardiomyocytes, the principle cell type of the heart, has been reported to be indirect. Here we have developed an inducible murine transgenic RA-reporter line using CreERT2 technology that permits lineage tracing of RA-responsive cells and faithfully recapitulates endogenous RA activity in multiple organs during embryonic development. Strikingly, we have observed a direct RA response in cardiomyocytes during mid-late gestation and after MI. Ablation of RA signaling through deletion of the Aldh1a1/a2/a3 genes encoding RA-synthesizing enzymes leads to increased cardiomyocyte apoptosis in adults subjected to MI. RNA sequencing analysis reveals Tgm2 and Ace1, two genes with well-established links to cardiac repair, as potential targets of RA signaling in primary cardiomyocytes, thereby providing novel links between the RA pathway and heart disease.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Tamoxifen, ≥99%
Sigma-Aldrich
Retinoic acid, ≥98% (HPLC), powder
Sigma-Aldrich
Trypsin from porcine pancreas, lyophilized powder, BioReagent, suitable for cell culture, 1,000-2,000 BAEE units/mg solid
Sigma-Aldrich
Corn oil, delivery vehicle for fat-soluble compounds
Roche
In Situ Cell Death Detection Kit, TMR red, sufficient for ≤50 tests