HomeCirculation ResearchVol. 127, No. 5In 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 published13 Aug 2020https://doi.org/10.1161/RES.0000000000000431Circulation Research. 2020;127:589is related toCritical Role of Neprilysin in Kidney Angiotensin MetabolismNovel Methods for Quantification of Vasodepression and Cardioinhibition During Tilt-Induced Vasovagal SyncopeSelf-Maintenance of Cardiac Resident Reparative Macrophages Attenuates Doxorubicin-Induced Cardiomyopathy Through the SR-A1-c-Myc AxisNeprilysin in Kidney Angiotensin Metabolism (p 593)In healthy kidneys, neprilysin keeps the renin-angiotensin system in balance, say Kalternecker et al.Download figureDownload PowerPointThe renin-angiotensin system (RAS) drives vasoconstriction, increased blood pressure and sodium retention in the kidneys, mainly via the action of angiotensin II (Ang II) and its receptor (AT1R). While the system is important for normal kidney function, excessive stimulation of AT1R leads to kidney damage. Angiotensin-(1-7), by contrast, drives vasodilation, reducing blood pressure and kidney damage (a so-called alternative RAS). While boosting Ang-(1-7) to counteract Ang II may seem like a potential treatment strategy for chronic kidney disease (CKD), the situation is complicated by the fact that Ang-(1-7) can actually be derived from Ang II, as well as from other precursors, and it isn’t clear which source of Ang-(1-7) predominates in kidneys. To find out, Kaltenecker and colleagues examined the abundance and activities of RAS and alternative RAS components in healthy and diseased kidney tissue. Using Ang I or Ang II as substrates, the team showed that, in healthy kidneys, Ang-(1-7) is mainly produced from Ang I via the action of an enzyme called neprilysin. In CKD tissue, Ang-(1-7) production is reduced relative to Ang II, the team also showed. These insights into RAS control in the renal system should help guide future therapies for CKD, the authors say.Self-Renewal of Local Macrophages Attenuates DiCM (p 610)Scavenger receptor SR-A1 promotes production of protective resident macrophages in doxorubicin-damaged hearts, say Zhang et al.Download figureDownload PowerPointThe chemotherapy drug doxorubicin (DOX) is effective against many types of cancer yet is damaging to the heart. The pathogenesis of DOX-induced cardiomyopathy (DiCM) is largely unknown, but accumulating evidence suggests inflammation, specifically the accumulation of macrophages, plays a critical role. Zhang and colleagues have now investigated the origins and features of cardiac macrophages during DiCM in greater detail. In mice treated with DOX, heart macrophages increased in abundance and originated from both the proliferation of resident cells and recruitment of monocyte-derived macrophages from the circulation, the team showed. These two cell populations differed in their characteristics, with those from the blood being mainly pro-inflammatory and resident cells having a reparative phenotype. The team also found that the resident macrophages exhibited an increased production of the scavenger receptor protein SR-A1 following DOX treatment, and that this receptor promoted the proliferation of the cells. Indeed, in mice lacking SR-A1 the pathology of DiCM was exacerbated. Together the results suggest that boosting the activity of these protective resident macrophages via SR-A1 augmentation may be a route to minimizing heart damage caused by DOX.Vasodepression and Cardioinhibition in VVS (p e126)van Dijk et al examine the precise cardiovascular events that precede fainting.Download figureDownload PowerPointSome people faint at the sight of blood or needles, or because they’ve stood up quickly after sitting or lying. Such individuals, who make up approximately one third of the population, have a condition known as vasovagal syncope (VVS)—thought to be caused by sudden drops in both blood pressure and heart rate. Recent evidence suggests a more complicated pre-fainting process, however, with reports that heart volume output is also reduced and that peripheral resistance—a factor affecting blood pressure—can both rise and fall. To determine the precise order and contribution of events prior to fainting, van Dijk and colleagues continuously monitored 163 patients as they underwent a tilt-table-test—a routine method for diagnosing VVS whereby a person’s position is changed from horizontal to upright. Blood pressure, heart output (stroke volume), and heart rate were all continuously assessed while patients were videoed to determine the precise timing of syncope. From averaging the results, the team determined that the initial and predominant contributing factor to fainting is a fall in the heart’s stroke volume, itself probably a result of blood pooling in the lower limbs when the patient is tilted upright. Why such reactions occur in some people and not others, however, was not investigated. Previous Back to top Next FiguresReferencesRelatedDetailsRelated articlesCritical Role of Neprilysin in Kidney Angiotensin MetabolismChristopher C. Kaltenecker, et al. Circulation Research. 2020;127:593-606Novel Methods for Quantification of Vasodepression and Cardioinhibition During Tilt-Induced Vasovagal SyncopeJ. Gert van Dijk, et al. Circulation Research. 2020;127:e126-e138Self-Maintenance of Cardiac Resident Reparative Macrophages Attenuates Doxorubicin-Induced Cardiomyopathy Through the SR-A1-c-Myc AxisHanwen Zhang, et al. Circulation Research. 2020;127:610-627 August 14, 2020Vol 127, Issue 5Article InformationMetrics Download: 194 © 2020 American Heart Association, Inc.https://doi.org/10.1161/RES.0000000000000431 Originally publishedAugust 13, 2020 PDF download
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