Abstract
HomeCirculation ResearchVol. 129, No. 4In This Issue Free AccessIn BriefPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyRedditDiggEmail Jump toFree AccessIn BriefPDF/EPUBIn This Issue Ruth Williams Ruth WilliamsRuth Williams Search for more papers by this author Originally published5 Aug 2021https://doi.org/10.1161/RES.0000000000000497Circulation Research. 2021;129:455is related toUnveiling Complexity and Multipotentiality of Early Heart Fieldsis related toCoronary Disease Association With ADAMTS7 Is Due to Protease ActivityDisrupted Resolution Mechanisms Favor Altered Phagocyte Responses in COVID-19Disrupted Resolution Mechanisms Favor Altered Phagocyte Responses in COVID-19 (p e54)Download figureDownload PowerPointKoenis et al show that dysregulation of inflammation-resolving factors is a feature of severe COVID-19.Inflammation is essential in the early stages of battling an invading pathogen, but can become damaging to the host if not resolved in a timely manner. Indeed, prolonged and unresolved inflammation is responsible for the hospitalizations and deaths of many COVID-19 patients. An excess of circulating pro-inflammatory cytokines is one feature of severe COVID-19, and now Koenis and colleagues show that certain pro-resolving factors are out of balance in such patients too. While blood samples from patients with mild COVID-19 revealed an increase in specialized pro-resolving lipid mediators (SPMs), those from patients with severe disease had lower levels of these lipid factors. Expression of SPM receptors on phagocytes was also higher in patients with mild disease than those with severe COVID-19. And, in line with this, the proportion of activated pro-inflammtory phagocytes was higher in patients with severe disease. The team went on to show that patients treated with the steroid dexamethasone had increased blood levels of SPMs. Together the results reveal SPMs are dysregulated in severe cases of COVID-19 and suggest SPM modulation, whether via steroid administration or other pharmacological means, could promote resolution of out-of-control inflammation.Coronary Disease Association with ADAMTS7 Is due to Protease Activity (p 458)Download figureDownload PowerPointCatalytic function of ADAMTS7 is needed for the enzyme’s pro-atherogenic activity, say Mizoguchi et al.Several genome-wide association studies (GWAS) have identified variants at the ADAMTS7 gene and its surrounding intergenic regions as risk loci for coronary artery disease. Furthermore, animal studies suggest the ADAMTS7 protein, which is both a metalloproteinase enzyme and a proteoglycan, is pro-atherogenic. However, which of the protein’s identities is responsible for promoting atherosclerosis is unclear. Mizoguchi and colleagues now show that the enzymatic function of ADAMTS7 is to blame. The team generated mice with [a] catalytically inactive version of ADAMTS7 and compared these animals with ones that either lacked ADAMTS7 entirely or had the fully intact protein (wild type). They found that loss of either ADAMTS7 protein itself or just its catalytic function was enough to reduce plaque burden in two different models of atherosclerosis. ADAMTS7 is known to regulate migration of vascular smooth muscle cells (VSMCs), which contributes to plaque formation, and VSMCs lacking either the full protein or just its catalytic activity had impaired migratory activity, the team showed. Together the results pinpoint ADAMTS7’s enzyme activity as pro-atherogenic and suggest the catalytic domain of the protein could be a therapeutic target for curtailing atherosclerosis.Unveiling Complexity and Multipotentiality of Early Heart Fields (p 474)Download figureDownload PowerPointZhang et al discover a shared source of mesodermal progenitors contributing to both the heart and extraembryonic tissues.The developing heart is thought to originate from two populations of cells—the first and second heart fields—which are first identifiable in the stage E7.5 mouse embryo (day 15 human embryo). Genes controlling the development of these fields have been linked to congenital heart defects (CHDs), but interestingly CHDs are also sometimes linked to placental abnormalities for reasons that are unclear. Zhang and colleagues now show that the first heart field and extraembryonic tissues—those which gives rise to the yolk sac and placenta—have an unexpected link. Through lineage-tracing experiments and single-cell transcriptomics, the team discovered that the first heart field consists of two sources of mesoderm progenitors—one that is embryonic in nature, and the other that arises from the interface between extraembryonic and embryonic tissues of the early gastrula. This latter population of progenitors, which expresses the transcription factor Hand1, gives rise to extraembryonic mesoderm cells in addition to heart field cells, the team showed. The finding of this shared source of mesodermal progenitors not only blurs the lines between the embryo and its supporting tissues, but may also explain the link between placental abnormalities and CHDs. Previous Back to top Next FiguresReferencesRelatedDetailsRelated articlesUnveiling Complexity and Multipotentiality of Early Heart FieldsQingquan Zhang, et al. Circulation Research. 2021;129:474-487Coronary Disease Association With ADAMTS7 Is Due to Protease ActivityTaiji Mizoguchi, et al. Circulation Research. 2021;129:458-470Disrupted Resolution Mechanisms Favor Altered Phagocyte Responses in COVID-19Duco Steven Koenis, et al. Circulation Research. 2021;129:e54-e71 August 6, 2021Vol 129, Issue 4Article InformationMetrics © 2021 American Heart Association, Inc.https://doi.org/10.1161/RES.0000000000000497 Originally publishedAugust 5, 2021 PDF download Advertisement
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