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HomeCirculation ResearchVol. 129, No. 8In 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 published30 Sep 2021https://doi.org/10.1161/RES.0000000000000511Circulation Research. 2021;129:767is related toYap Promotes Noncanonical Wnt Signals From Cardiomyocytes for Heart RegenerationEpigenetic Age Acceleration Reflects Long-Term Cardiovascular HealthNonbone Marrow CD34+ Cells Are Crucial for Endothelial Repair of Injured ArteryCardiovascular Health and Epigenetic Age (p 770)DNA methylation status indicates future risk of cardiovascular issues, say Joyce et al.Download figureDownload PowerPointDNA methylation is an epigenetic modification that regulates gene transcription. Studies of young and old individuals have shown that, at certain locations in the genome, methylation status is highly correlated with age. However, such methylation patterns are also linked to measures of cardiovascular health (CVH) including blood pressure, cholesterol level and body-mass index. This means, if a person has particularly good or poor CVH, their DNA may appear younger or older than it actually is. Joyce and colleagues hypothesized that people with poor CVH might exhibit faster methylation changes than those with good CVH. If so, DNA methylation patterns might be useful for predicting future cardiovascular risk. The team examined DNA methylation in over 1000 individuals enrolled in a prospective heart health cohort, testing them at around age 40 and again at around 45. Changes in methylation status were then tallied against the individuals’ CVH scores over a longer period. Sure enough, faster epigenetic changes did correlate with poorer CVH in later life. Data from a second cohort supported the findings. The authors thus conclude that DNA methylation status may be an early biomarker of cardiovascular issues and may allow for prompt implementation of treatment and prevention strategies.Wls Suppresses Fibrosis in Heart Regeneration (p 782)Yap-to-Wntless pathway promotes regeneration in newborn mouse hearts, report Liu et al.Download figureDownload PowerPointAfter a heart attack, scores of cardiomyocytes are destroyed and replaced with a fibrotic scar that interferes with contractile function. While adult mouse and human hearts are similar in this regard, the hearts of newborn mice possess potent regenerative capacity that persists for approximately a week. The transcription factor Yap is known to regulate this regenerative process since its deletion in neonatal cardiomyocytes eliminates heart regeneration and its over-activation in adult cardiomyocytes reduces fibrosis. Because these findings suggest cardiomyocytes transmit signals to cardiac fibroblasts, and because Wntless is both a regulator of signal secretion and a target of Yap, Liu and colleagues made mice that lacked Wntless in their cardiomyocytes. They found that, while the mice appeared to have normal heart development and function, their neonatal regenerative capacity was impaired. Indeed, in the weeks after a heart injury, the test mice had reduced heart function, increased scar size and increased numbers of activated cardiac fibroblasts compared with that seen in control animals. By identifying Wntless as a key piece of the regeneration machinery, the work will likely inform future strategies aimed at minimizing scarring after heart attacks, say the authors.CD34+ Cells in Vascular Disease (p e146)Progenitors in blood vessel walls contribute to endothelial repair, say Jiang et al.Download figureDownload PowerPointInjury to the endothelial wall of a blood vessel can occur as a result of atherosclerosis or angioplasty procedures such as stent insertion. In the hopes of repairing such injuries there have been a number of trials involving administration of endothelial progenitor cells (EPCs)—circulating cells displaying the surface protein CD34. But, these trials have had variable outcomes leading to debate over the nature and identity of EPCs. Furthermore, cells displaying CD34 are also found in bone marrow and in blood vessel walls themselves. Reasoning that the vessel wall CD34-positive cells may have vessel healing potential, Jiang and colleagues examined this population more closely. Using lineage tracing experiments in mouse blood vessels, the team found wall-resident CD34 cells did indeed acquire an endothelial fate upon vessel injury, while CD34 cells from bone marrow acquired immune cell identities. Furthermore, when the team ablated CD34 cells from vessel walls, vessel injuries were exacerbated. The team went on to identify a microRNA-regulated pathway controlling endothelial fate in the resident CD34 cells. With this detailed understanding of the cells and molecules controlling vessel repair, say the team, there will be greater opportunity for developing vessel-healing treatments. Previous Back to top Next FiguresReferencesRelatedDetailsRelated articlesYap Promotes Noncanonical Wnt Signals From Cardiomyocytes for Heart RegenerationShijie Liu, et al. Circulation Research. 2021;129:782-797Epigenetic Age Acceleration Reflects Long-Term Cardiovascular HealthBrian T. Joyce, et al. Circulation Research. 2021;129:770-781Nonbone Marrow CD34+ Cells Are Crucial for Endothelial Repair of Injured ArteryLiujun Jiang, et al. Circulation Research. 2021;129:e146-e165 October 1, 2021Vol 129, Issue 8Article InformationMetrics Download: 298 © 2021 American Heart Association, Inc.https://doi.org/10.1161/RES.0000000000000511 Originally publishedSeptember 30, 2021 PDF download