Abstract

HomeCirculation ResearchVol. 123, No. 10In This Issue Free AccessIn BriefPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessIn BriefPDF/EPUBIn This Issue Ruth Williams Ruth WilliamsRuth Williams Search for more papers by this author Originally published25 Oct 2018https://doi.org/10.1161/RES.0000000000000238Circulation Research. 2018;123:1103is related toLack of Cardiac Improvement After Cardiosphere-Derived Cell Transplantation in Aging Mouse Heartsis related toTranscriptome Analysis Reveals Nonfoamy Rather Than Foamy Plaque Macrophages Are Proinflammatory in Atherosclerotic Murine ModelsMicrobial Transplantation With Human Gut Commensals Containing CutC Is Sufficient to Transmit Enhanced Platelet Reactivity and Thrombosis PotentialTranscriptome of Atherosclerotic Macrophages (p 1127)Download figureDownload PowerPointNonfoamy plaque macrophages are more proinflammatory than their foamy counterparts, report Kim et al.Atherosclerosis is characterized by the deposition of fat and the accumulation of immune cells such as macrophages in the vessel wall. These macrophages phagocytose the lipid particles and ultimately turn into fat-filled foam cells. Given this central role of macrophages in atherosclerosis, Kim and colleagues wanted to investigate their characteristics more thoroughly. To that end, they developed a new flow-cytometry technique that could distinguish between nonfoamy plaque macrophages (those that have accumulated little to no lipids) and fully lipid-laden foamy cells. They separated these two populations of macrophages by differences in their granularity and fluorescent labeling by the lipid probe BODIPY493/503, and compared their transcriptomes. They found that nonfoamy macrophages tended to express high levels of proinflammatory genes, while foamy macrophages had high levels of genes involved in lipid processing and as well as the resolution of inflammation. The team also confirmed the results obtained with mouse cells in human plaque macrophages, showing that the nonfoamy cell population was markedly proinflammatory.CDC Transplantation in Aging Mouse Hearts (p e21)Download figureDownload PowerPointCardiosphere-derived cells do not improve heart function in aged mice, say Zhao et al.Several clinical and preclinical studies are currently evaluating the potential of different cell types for promoting the repair and regeneration of injured and aged heart tissue. Of the candidate cells under consideration, cardiosphere-derived cells (CDCs), which are balls of cells that form during ex vivo culture of myocardial tissue, have been shown capable of differentiating into all three major cell types of the heart: cardiac myocytes, endothelium, and smooth muscle cells. Although recent work has shown that in aged rats CDCs can improve myocardial performance, Zhao and colleagues now report that this result is not reproducible in aged mice, where intramyocardial injections of CDCs provided no perceivable benefits over control treatments. To test the effects of CDCs, Zhao et al injected these cells in the left ventricles of nineteen 21-month-old mice. A separate group of 15 mice received control injections of phosphate-buffered saline. A month after these treatments, there was no difference between these two groups in terms of their left ventricle function, exercise capacity, or other markers of myocardial health. In view of the inconsistent results obtained with CDCs, the authors advise that further preclinical evaluation with these cells may be required to determine their efficacy.Microbial Transplantation Confers Thrombosis Risk (p 1164)Download figureDownload PowerPointGut microbes containing the gene cutC confer thrombosis risk, report Skye et al.Transfer of gut microbes from one organism to another can, in some cases, lead to the transfer of phenotypes, such as disease susceptibility. It is thought that the metabolites produced by the microbes somehow affect host physiology. Indeed, one such bacterial metabolite—trimethylamine N-oxide (TMAO)—has been linked to an increase in platelet reactivity, thrombosis risk, and cardiovascular disease risk in animal models and humans. The microbial gene responsible for the production of TMA (which gets converted to TMAO in the host liver) has been identified, but whether the presence of this gene—cutC—in human microbial specimens is sufficient to affect thrombosis has not been demonstrated. Skye and colleagues now show that mice that received an oral dose of a defined set of human gut microbes—all of which lacked cutC—did not exhibit increased platelet activation and thrombosis, while the addition of just one species containing cutC to that microbial set heightened platelet aggregation in the recipient mice. Together, these results provide further evidence that microbial TMA is linked to thrombosis risk and suggest that targeting cutC or TMA may be a novel avenue for preventing or treating cardiovascular disease. Previous Back to top Next FiguresReferencesRelatedDetailsRelated articlesLack of Cardiac Improvement After Cardiosphere-Derived Cell Transplantation in Aging Mouse HeartsZhen-Ao Zhao, et al. Circulation Research. 2018;123:e21-e31Transcriptome Analysis Reveals Nonfoamy Rather Than Foamy Plaque Macrophages Are Proinflammatory in Atherosclerotic Murine ModelsKyeongdae Kim, et al. Circulation Research. 2018;123:1127-1142Microbial Transplantation With Human Gut Commensals Containing CutC Is Sufficient to Transmit Enhanced Platelet Reactivity and Thrombosis PotentialSarah M. Skye, et al. Circulation Research. 2018;123:1164-1176 October 26, 2018Vol 123, Issue 10 Advertisement Article InformationMetrics © 2018 American Heart Association, Inc.https://doi.org/10.1161/RES.0000000000000238 Originally publishedOctober 25, 2018 PDF download Advertisement

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