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HomeCirculation ResearchVol. 130, 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 published3 Mar 2022https://doi.org/10.1161/RES.0000000000000536Circulation Research. 2022;130:691is related toEro1α-Dependent ERp44 Dissociation From RyR2 Contributes to Cardiac ArrhythmiaGLP1R Attenuates Sympathetic Response to High Glucose via Carotid Body InhibitionInhibition of IL11 Signaling Reduces Aortic Pathology in Murine Marfan SyndromeGLP1R Attenuates Sympathetic Response to High Glucose via Carotid Body Inhibition (p 694)Gut hormone receptors in the carotid body may be treatment targets for metabolic syndrome, say Pauza et al.Download figureDownload PowerPointHypertension and diabetes are risk factors for cardiovascular disease (CVD) and yet, for many patients with these two conditions, lowering blood pressure and blood sugar is insufficient for eliminating the risk. Because both hypertension and diabetes are linked to increased sympathetic nerve activation, and because the carotid body (CB)—a clusters of sensory cells in the carotid artery—regulates sympathetic nerve activity, Pauza and colleagues investigated the CB’s possible involvement. They performed a transcriptome analysis of CB tissue from rats with and without spontaneous hypertension and found, among many differently expressed genes, that the transcript encoding glucagon-like peptide-1 receptor (GLP1R) was considerably less abundant in the hypertensive animals. This was of particular interest because the gut hormone GLP1 promotes insulin secretion and tends to be suppressed in type 2 diabetes. Moreover, GLP1R agonists are already used as diabetes treatments. The team now show that treating rat CBs with such an agonist suppresses sympathetic nerve activation and arterial blood pressure, suggesting such drugs may provide benefits in more ways than one, and that the CB could be a novel target for lowering CVD risk in metabolic syndrome.Ero1α-Dependent ERp44 Dissociation from RyR2 Contributes to Cardiac Arrhythmia (p 711)Blocking oxidoreductase Ero1α could reduce arrhythmia risk in cardiovascular disease, say Hamilton et al.Download figureDownload PowerPointThe oxidative stress associated with cardiovascular disease (CVD) can lead to heart arrhythmia and sudden death. At the cellular level, the increased oxidation in the sarcoplasmic reticulum (SR) triggers aberrant release of calcium—via the ryanodine receptor (RyR2) channel—and this in turn ramps up muscle contractions. However, the precise molecular details of the pathology are lacking. Cellular stress is known to raise the level of SR oxidoreductase Ero1α, which interacts with an inhibitor of calcium release called ERp44. Now, Hamilton and colleagues complete the molecular puzzle, showing that ERp44 normally binds and inhibits RyR2 in rat cardiomyocytes. The stress-induced increase in Ero1α expression (in hypertrophic rat cardiomyocytes) causes dissociation of ERp44 from RyR2, they report, thus boosting calcium release. Importantly, the team also showed that inhibiting Ero1α reduced oxidation in the SR, prevented ERp44-RyR2 disassociation and reduced RyR2-mediated calcium release. It also curbed arrhythmia in isolated hypertrophic hearts. Because myocardium from heart failure patients also exhibited increased Ero1α expression compared with controls, the authors say, Ero1α inhibition could be a clinical strategy for preventing CVD-associated arrhythmia.Inhibition of IL11 Signaling Reduces Aortic Pathology in Murine Marfan Syndrome (p 728)Lim et al suggest cytokine IL-11 as a new target for the treatment of Marfan syndrome.Download figureDownload PowerPointPeople with the genetic connective tissue disorder Marfan syndrome (MFS) are typically tall and thin with long limbs, and are prone to skeletal, eye and cardiovascular problems including a life-threatening weakening of the aorta. While MFS patients commonly take blood-pressure lowering treatments to minimize the risk of aortic aneurysm and dissection, there is no cure for MFS nor even a targeted therapy. With the aim of finding novel MFS treatments, Lim and colleagues focused their attention on IL-11. This cytokine is strongly induced in vascular smooth muscle cells (VSMCs) upon treatment with the growth factor TGFβ—itself overactivated in MFS patients and considered a key feature of the syndrome’s molecular pathology. The team now show that IL-11 is indeed strongly upregulated in the aortas of MFS model mice and that genetically eliminating IL-11 in these animals can protect them against the aortic pathology they normally exhibit—including dilation, fibrosis, inflammation, elastin degradation and loss of VSMCs. Furthermore, treating MFS mice with an anti-IL-11 neutralizing antibody had the same beneficial effects. The results therefore suggest that inhibiting IL-11 activity could be a novel approach for protecting the aortas of MFS patients. Previous Back to top Next FiguresReferencesRelatedDetailsRelated articlesEro1α-Dependent ERp44 Dissociation From RyR2 Contributes to Cardiac ArrhythmiaShanna Hamilton, et al. Circulation Research. 2022;130:711-724GLP1R Attenuates Sympathetic Response to High Glucose via Carotid Body InhibitionAudrys G. Pauza, et al. Circulation Research. 2022;130:694-707Inhibition of IL11 Signaling Reduces Aortic Pathology in Murine Marfan SyndromeWei-Wen Lim, et al. Circulation Research. 2022;130:728-740 March 4, 2022Vol 130, Issue 5Article InformationMetrics © 2022 American Heart Association, Inc.https://doi.org/10.1161/RES.0000000000000536 Originally publishedMarch 3, 2022 PDF download Advertisement