Effects of vitamin A deficiency in the postnatal mouse heart: role of hepatic retinoid stores

Abstract

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, agematched, 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.heart; lecithin retinyl acyl transferase; postnatal; retinoic acid; vitamin A NEW & NOTEWORTHYWe demonstrate heart-wide expression of retinoic acid receptor-␥, a retinoic acid-activated nuclear receptor, and report that ventricles from adult mice with depleted hepatic vitamin A stores have altered gene expression, a significant increase in proliferating progenitor cells, and improved response to acute myocardial injury.

Guidelines for measuring cardiac physiology in mice

“…To evaluate the current reporting of echocardiographic results, we accessed PubMed on July 21, 2017, and searched for “mouse and American Journal of Physiology and (echocardiography or echocardiographic or ultrasound).” This search resulted in 437 articles, of which 52 articles were published between January 1, 2016, and present as well as 14 articles that were excluded as false positives (two kidney, one liver, one lung, one bone, one RV, two rat not mouse, one fetal not adult, and five with no cardiac echocardiography results). The remaining 38 articles were analyzed both for completeness of information provided and for quality assessment of the echocardiography values reported ( 11 , 13 , 22 , 27 , 30 , 36 , 38 , 39 , 42 , 45 , 52 , 54 , 57 , 59 , 65 , 70 , 75 , 76 , 78 , 85 , 102 , 114 , 117 – 119 , 132 , 147 , 148 , 158 , 160 , 165 , 170 , 172 , 182 , 187 , 193 , 201 , 206 ).…”

ErbB2 promotes endothelial phenotype of human left ventricular epicardial highly proliferative cells (eHiPC)

“…Although the exact mechanisms are still under investigation, the published data indicate that inhibition of ErbB2 results in increased generation of reactive oxygen species (28, 41) , downregulation of pro-survival PI3K/AKT signaling (48) and improper functioning of excitation–contraction coupling machinery and loss of contractile function (44) . Recently, we have shown that endothelial cells represent one of the major subpopulations of proliferating cells in the adult heart (3) , indicating endothelial renewal in vivo . Our current findings suggest that ErbB2-targeted therapy may prevent endothelial differentiation of highly proliferative cells and perhaps contribute to endothelial dysfunction and development of cardiomyopathy (29) .…”

Modulation of retinoid signaling: therapeutic opportunities in organ fibrosis and repair

“…In mouse models of obesity, atRA-treatment prevented fibrosis and cardiomyocyte apoptosis (Manolescu et al, 2014). Conversely, in rodent models of myocardial infarction, vitamin A insufficiency was associated with adverse ventricular remodeling (Asson-Batres et al, 2016;Minicucci et al, 2010). These observations are also supported by evidence that mice deficient in β-carotene-15,15'-dioxygenase (BCO1), the enzyme required to convert provitamin A carotenoids to retinol, also exhibit systolic dysfunction (Hessel et al, 2007;S.…”