Aim: 

Retinoic acid has profound effects on cell proliferation and differentiation. This study evaluates if the nuclear retinoic acid receptors (RAR) are activated in acute myocardial ischemia and post ischemic remodelling and if so, when and in which cardiac cells.

Methods: 

In order to investigate cardiac activation of RAR in vivo, RARE-luciferase reporter mice were subjected to myocardial infarction or sham operated. Luciferase activity was imaged serially in a CCD camera up to 6 weeks postinfarction, while other mice were collected for evaluation of target gene expression with real time PCR. One week postoperatively, organs were harvested from additional mice for ex vivo imaging. Cardiomyocytes and cardiofibroblasts were isolated from the infarcted and uninfarcted regions of myocardium, and luciferase activity analyzed in vitro.

Results: 

RARE-luciferase activity was higher in the thoracic region of infarcted mice than in sham operated. The activity peaked at the 7th post operative day and thereafter gradually declined during the process of remodelling. Ex vivo luminescent imaging of explanted organs one week post-operatively confirmed that increased RAR activation was exclusively in the heart. In accordance, infarcted RARE-luciferase reporter mice had increased cardiac expression of RAR-responsive genes. In vitro analyses of luciferase activity in cardiomyocytes and cardiofibroblasts revealed increased RAR activity in cardiofibroblasts from the infarcted myocardium.

Conclusion: 

Cardiac RAR are activated in the acute/early remodeling stages postinfarction, where the largest contribution appears to be from cardiofibroblasts in the infarcted myocardium. RAR activation may play a role in remodeling after acute myocardial infarction.