PMID:20097747

Citation	Lionetti, V, Cantoni, S, Cavallini, C, Bianchi, F, Valente, S, Frascari, I, Olivi, E, Aquaro, GD, Bonavita, F, Scarlata, I, Maioli, M, Vaccari, V, Tassinari, R, Bartoli, A, Recchia, FA, Pasquinelli, G and Ventura, C (2010) Hyaluronan mixed esters of butyric and retinoic acid affording myocardial survival and repair without stem cell transplantation. J. Biol. Chem. 285:9949-61
Abstract	Possible cardiac repair by adult stem cell transplantation is currently hampered by poor cell viability and delivery efficiency, uncertain differentiating fate in vivo, the needs of ex vivo cell expansion, and consequent delay in transplantation after the onset of heart attack. By the aid of magnetic resonance imaging, positron emission tomography, and immunohistochemistry, we show that injection of a hyaluronan mixed ester of butyric and retinoic acid (HBR) into infarcted rat hearts afforded substantial cardiovascular repair and recovery of myocardial performance. HBR restored cardiac [(18)F]fluorodeoxyglucose uptake and increased capillary density and led to the recruitment of endogenous Stro-1-positive stem cells. A terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling assay demonstrated that HBR-treated hearts exhibited a decrease in the number of apoptotic cardiomyocytes. In isolated rat cardiomyocytes and Stro-1 stem cells, HBR enhanced the transcription of vascular endothelial growth factor, hepatocyte growth factor, kdr, akt, and pim-1. HBR also increased the secretion of vascular endothelial growth factor and hepatocyte growth factor, suggesting that the mixed ester may have recruited both myocardial and Stro-1 cells also. An increase in capillarogenesis was induced in vitro with medium obtained from HBR-exposed cells. In the infarcted myocardium, HBR injection increased histone H4 acetylation significantly. Acetyl-H4 immunoreactivity increased in rat cardiomyocytes and Stro-1 cells exposed to HBR, compared with untreated cells. In conclusion, efficient cardiac regenerative therapy can be afforded by HBR without the need of stem cell transplantation or vector-mediated gene delivery.
Links	PubMed PMC2843241 Online version:10.1074/jbc.M109.087254
Keywords	Animals; Butyric Acid/chemistry; Cell Survival; Fluorodeoxyglucose F18/metabolism; Gene Transfer Techniques; Hyaluronic Acid/chemistry; Magnetic Resonance Imaging/methods; Male; Myocardial Infarction/metabolism; Myocardium/cytology; Myocardium/metabolism; Myocytes, Cardiac/metabolism; Neovascularization, Pathologic; Positron-Emission Tomography/methods; Rats; Rats, Wistar; Stem Cell Transplantation/methods; Tretinoin/chemistry; Tretinoin/metabolism
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
RAT:AKT1	involved_in	GO:0030212: hyaluronan metabolic process	ECO:0000270: expression pattern evidence used in manual assertion		P		Seeded From UniProt	complete

References

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