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HomeCirculation ResearchVol. 118, No. 1In This Issue Free AccessResearch ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessResearch ArticlePDF/EPUBIn This Issue Ruth Williams Ruth WilliamsRuth Williams Search for more papers by this author Originally published8 Jan 2016https://doi.org/10.1161/RES.0000000000000091Circulation Research. 2016;118:2VEGF-Induced miR-17–92 Expression in Angiogenesis (p 38)Download figureDownload PowerPointVEGF activates microRNA cluster miR-17–92 to promote angiogenesis, report Chamorro-Jorganes et al.Vascular endothelial growth factor (VEGF) is a key promoter of angiogenesis, regulating the proliferation, migration and survival of endothelial cells (ECs). In these cells, VEGF also increases the expression of a cluster of seven microRNAs, miR-17–92, however, the pathway to miR-17–92 activation remain unclear and it is not known whether this activation promotes angiogenesis. Indeed, previous analyses of individual miRs from this cluster have suggested some of these miRs might even suppress angiogenesis. Chamorro-Jorganes and colleagues have now discovered that in human and mouse ECs, VEGF upregulates all seven miRs together via the transcription factor ELK1. They showed that the promoter region of miR-17–92 binds ELK1, and that deletion of this binding site or suppression of ELK1 itself prevented VEGF-induced miR-17–92 expression. The team created transgenic mice with an EC-specific miR-17–92 inactivation. They showed that in the postnatal retina, adult ear, and a tumor model, inhibition of miR-17–92 prevented normal VEGF-induced angiogenesis. Together, the work reveals that ELK1-mediated expression of the miR-17–92 cluster promotes angiogensis in a number of VEGF-regulated processes.Human Myocardium on Native Extracellular Matrix (p 56)Download figureDownload PowerPointGuyette et al seed whole human heart scaffolds with human iPSC-derived cardiomyocytes.More than 5 million people in the US suffer from heart failure, and many urgently require transplants. Donor hearts are scarce, however, and even the lucky patients that do receive hearts face rejection risks and complications due to immunosuppressive therapy. The development of induced pluripotent stem cell (iPSC) techniques, which enable a patient’s own cells to be reprogrammed into cardiomyocytes, holds the promise of growing patient-specific myocardium for transplant. But ensuring such engineered tissue has the right architecture, flexibility and vascular supply is no small feat. Guyette and colleagues have now taken a significant new step in the right direction. Using some of the many thousands of donor hearts unsuitable for transplantation, they made cell-free whole heart scaffolds—by perfusing the organs with decellularization solutions. In parallel, they grew vast numbers of human cardiomyocytes from iPSCs. They then seeded the cells onto scaffold sections as well as fully intact decellularized hearts. The tissue sections exhibited spontaneous contractions within a week, while the partially reseeded whole hearts, upon electrical stimulation, produced visible contractions and generated left ventricle pressure. Though much work remains before such tissues could be used clinically, the study hints that such an approach may be achievable at a clinical scale.Cardiac Myocyte-Specific Cell Cycle Indicator (p 20)Download figureDownload PowerPointHirai et al develop transgenic mice for monitoring heart cell proliferation.The neonatal heart has a tremendous capacity for regeneration, but the adult heart does not. This is in part because adult cardiomyocytes, unlike their neonatal counterparts, have little to no proliferative capacity. Therefore understanding the processes that control cardiomyocyte proliferation and how these processes could be re-activated in the adult heart would be of great value to the development of future regenerative therapies. Studying cardiomyocyte proliferation is not straightforward, however, because even though there are makers for identifying proliferating cells or for identifying cardiomyocytes, there are no specific markers for identifying proliferating cardiomyocytes. To develop such a biomarker, Hirai and colleagues engineered mice to carry a transgene encoding a cell cycle protein called cyclinA2 that could fuse to a green fluorescent protein. The fusion and thus the fluorescence, however, could only occur in cells expressing the enzyme cre recombinase. Crossing the cyclinA2 transgenic mice with ones expressing cre recombinase specifically in cardiomyocytes thus resulted in mice in which only the proliferating cardiomyocytes glow green. Using these mice the team made some unexpected discoveries, including the observation that, in newborn mice, myocyte proliferation was more abundant in the left rather than the right ventricle—perhaps explaining why the right ventricle is smaller. Previous Back to top Next FiguresReferencesRelatedDetails January 8, 2016Vol 118, Issue 1 Advertisement Article InformationMetrics © 2016 American Heart Association, Inc.https://doi.org/10.1161/RES.0000000000000091 Originally publishedJanuary 8, 2016 PDF download Advertisement