Effects of vitamin A deficiency in the postnatal mouse heart: role of hepatic retinoid stores.
Maine Medical Center Research Institute
American journal of physiology. Heart and circulatory physiology
Acyltransferases, Animals, Echocardiography, Heart, Liver, Mice, Mice, Knockout, Myocardial Infarction, Myocardium, Receptors, Retinoic Acid, Retinoids, Vitamin A Deficiency
To determine whether hepatic depletion of vitamin A (VA) stores has an effect on the postnatal heart, studies were carried out with mice lacking liver retinyl ester stores fed either a VA-sufficient (LRVAS) or VA-deficient (LRVAD) diet (to deplete circulating retinol and extrahepatic stores of retinyl esters). There were no observable differences in the weights or gross morphology of hearts from LRVAS or LRVAD mice relative to sex-matched, age-matched, and genetically matched wild-type (WT) controls fed the VAS diet (WTVAS), but changes in the transcription of functionally relevant genes were consistent with a state of VAD in LRVAS and LRVAD ventricles. In silico analysis revealed that 58/67 differentially expressed transcripts identified in a microarray screen are products of genes that have DNA retinoic acid response elements. Flow cytometric analysis revealed a significant and cell-specific increase in the number of proliferating Sca-1 cardiac progenitor cells in LRVAS animals relative to WTVAS controls. Before myocardial infarction, LRVAS and WTVAS mice had similar cardiac systolic function and structure, as measured by echocardiography, but, unexpectedly, repeat echocardiography demonstrated that LRVAS mice had less adverse remodeling by 1 wk after myocardial infarction. Overall, the results demonstrate that the adult heart is responsive to retinoids, and, most notably, reducing hepatic VA stores (while maintaining circulating levels of VA) impacts ventricular gene expression profiles, progenitor cell numbers, and response to injury.
Asson-Batres, Mary Ann; Ryzhov, Sergey; Tikhomirov, Oleg; Duarte, Christine W; Congdon, Clare Bates; Lessard, Craig R; McFarland, Samuel; Rochette-Egly, Cecile; Tran, Truc-Linh; Galindo, Cristi L; Favreau-Lessard, Amanda J; and Sawyer, Douglas B, "Effects of vitamin A deficiency in the postnatal mouse heart: role of hepatic retinoid stores." (2016). Maine Medical Center. 1721.