HomeCirculation ResearchVol. 127, No. 12In 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 published3 Dec 2020https://doi.org/10.1161/RES.0000000000000452Circulation Research. 2020;127:1469is related toArterial Stiffness Preceding DiabetesTamoxifen Accelerates Endothelial Healing by Targeting ERα in Smooth Muscle CellsATAC-Seq Reveals an Isl1 Enhancer That Regulates Sinoatrial Node Development and FunctionTamoxifen and E2 Effects on Reendothelialization (p 1473)Zahreddine et al investigate Tamoxifen’s vasculoprotective effects.Download figureDownload PowerPointFor breast cancers that contain high levels of estrogen receptor, a standard treatment is to give drugs that block either estrogen production, or the receptor itself, such as Tamoxifen. Eliminating the vasculoprotective effects of estrogen might increase the risk of cardiovascular disease. But because Tamoxifen can antagonize or activate the receptor depending on the tissue, its role in such risk is unclear. Some evidence even suggests it might have protective effects, such as promoting vascular endothelial healing. Zahreddine and colleagues now show that while mice suffering endovascular injury—damage to the inside of a blood vessel—have improved healing when treated with Tamoxifen or with estrogen, those suffering pervascular injury—which also affects the surrounding smooth muscle—heal only in response to estrogen. This suggested Tamoxifen’s healing effect might require smooth muscle cells (SMCs). Sure enough, mice lacking the estrogen receptor in SMCs, healed endovascular injuries in response to the hormone but not Tamoxifen, while mice lacking the receptor in endothelial cells, healed such injuries in response to Tamoxifen but not estrogen. The work reveals nuance in the molecular actions of Tamoxifen that should inform future assessments of its risks and benefits, say the authors.Arterial Stiffness Preceding Diabetes (p 1491)Having stiffer arteries may increase a person’s risk for diabetes, say Zheng et al.Download figureDownload PowerPointAs a person ages, their risk of developing diabetes and cardiovascular disease increases. Aging is also linked to increasing arterial stiffness and high blood pressure, but how all these individual conditions affect and influence each other is not entirely clear. For example, while arterial stiffness and diabetes tend to correlate, whether one increases the risk for the other, or the risk relationship is bidirectional, is not known. To find out, Zheng and colleagues studied diabetes and arterial stiffness in a cohort of 8,956 Chinese people between 2010 and 2015, none of whom had diabetes or cardiovascular disease at the outset. With repeated measures of fasting glucose levels—as an indicator of diabetes—and pulse wave velocity—as a measure of arterial stiffness—the team found that participants with a higher baseline arterial stiffness were more likely to develop diabetes during the five-year period than those with lower stiffness. A total of 979 individuals developed diabetes during the study. Higher baseline glucose levels did not predict future arterial stiffness, however, suggesting the risk relationship is one-way. While the results require confirmation in further cohorts, they also set the stage for investigations into pathological mechanisms linking arterial stiffness to diabetes.ATAC-seq Identifies Novel Isl1 SAN Enhancer (p 1502)Galang et al discover a novel sinoatrial node enhancer element.Download figureDownload PowerPointPacemaker cells (PCs) of the sinoatrial node establish and control the rhythmic contractions of the heart. These cells differ from regular cardiomyocytes in their transcription profiles, but how this transcriptional fate is established and maintained is not fully understood. To investigate the epigenetic landscape defining PC fate, Galang and colleagues have employed a technique called ATAC-seq, which identifies areas of the genome with accessible, open chromatin structures—an indication of transcriptional activity. The team compared the genomes of PCs and atrial cardiomyocytes and found a number of PC-specific accessible loci that had both large numbers of transcription factor binding sequences and enhancer activity when assayed in mice. The team went on to specifically characterize one novel enhancer upstream of the gene encoding Isl1—a key transcription factor for PC identity. They showed that deleting the enhancer caused underdevelopment of the sinoatrial node and arrhythmias in mice. They also noted that single nucleotide polymorphisms at the equivalent locus in humans had been linked to variations in resting heart rate. The report verifies ATAC-seq as an effective tool for identifying PC enhancers, and will launch further studies into how such enhancers function in heart development and disease. Previous Back to top Next FiguresReferencesRelatedDetailsRelated articlesArterial Stiffness Preceding DiabetesMengyi Zheng, et al. Circulation Research. 2020;127:1491-1498Tamoxifen Accelerates Endothelial Healing by Targeting ERα in Smooth Muscle CellsRana Zahreddine, et al. Circulation Research. 2020;127:1473-1487ATAC-Seq Reveals an Isl1 Enhancer That Regulates Sinoatrial Node Development and FunctionGiselle Galang, et al. Circulation Research. 2020;127:1502-1518 December 4, 2020Vol 127, Issue 12Article InformationMetrics Download: 308 © 2020 American Heart Association, Inc.https://doi.org/10.1161/RES.0000000000000452 Originally publishedDecember 3, 2020 PDF download
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