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HomeCirculation ResearchVol. 123, No. 11In This Issue Free AccessIn BriefPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessIn BriefPDF/EPUBIn This Issue Ruth Williams Ruth WilliamsRuth Williams Search for more papers by this author Originally published8 Nov 2018https://doi.org/10.1161/RES.0000000000000240Circulation Research. 2018;123:1177is related toGDF11 Decreases Pressure Overload–Induced Hypertrophy, but Can Cause Severe Cachexia and Premature Deathis related toMacrophage Inflammation, Erythrophagocytosis, and Accelerated Atherosclerosis in Jak2V617F MiceA Miniaturized, Programmable Pacemaker for Long-Term Studies in the MouseProgrammable Mouse Pacemaker (p 1208)Download figureDownload PowerPointHulsmans et al have created a tiny programmable pacemaker for mice.Implantable electronic pacemakers can be lifesaving. They improve quality of life for patients with arrhythmia due to heart failure or other causes. However, not all patients respond equally well, and sometimes pacemakers can even cause cardiomyopathy. Therefore, a better understanding of the effects of pacemakers during different cardiac pathologies is needed. Although several mouse models for heart failure and arrhythmias are available, there is a lack of long-term pacing technologies that could be used in small animals. Therefore, Hulsmans and colleagues built a programmable, battery-powered pacemaker for freely moving mice that could remain operational for months. Adapted from the smallest clinical pacemaker available, the team’s new device, once surgically implanted, can be used to both monitor the effects of pacing on a diseased heart and to analyze pacing-induced myopathy. Using this device, the team could successfully treat mice with complete atrioventricular block. They also found that rapid ventricular pacing in healthy animals could lead to myocardial fibrosis, inflammation, and myopathy. The new device could enable researchers to study the positive and negative outcomes of pacemakers, which could lead to further clinical optimization for use in patients with arrhythmias.Jak2V617F Promotes Atherosclerosis (p e35)Download figureDownload PowerPointMutation to Janus kinase 2 prompts clonal hematopoiesis and acceleration of atherosclerosis in model mice, report Wang et al.Clonal hematopoiesis (CH)—the clonal expansion of certain subpopulations of blood cells—is associated with both myeloproliferative neoplasms (blood cancers) and an increased risk of athero-thrombotic disease. Commonly observed in elderly patients, CH can be caused by mutations to any one of a handful of genes, including JAK2—the gene encoding cell signaling factor Janus kinase 2. To examine the mechanisms linking CH to athero-thrombosis, Wang and colleagues studied atherosclerosis-prone mice in which bone marrow cells carried a known CH-associated JAK2 mutation. After several weeks on a Western diet, the mutation-carrying mice showed accelerated atherosclerosis with advanced lesions that displayed increased necrotic core size and reduced clearance of dead cells. Macrophages of the mutant mice had increased expression of proinflammatory cytokines, whereas, their red blood cells were more susceptible to phagocytosis by macrophages. These defects in erythrocytes and macrophages could, in part, be responsible for the accumulation of iron in plaques, defective clearance of dead cells, and increased inflammation in the lesions. Together, the team’s work confirms the role of the JAK2 mutation in CH-linked atherogenesis and provides a model system for further CH studies.GDF11 Decreases Hypertrophy but Causes Cachexia (p 1220)Download figureDownload PowerPointBoosting GDFII improves hypertrophy but causes severe muscle wasting, say Harper et al.Cardiac hypertrophy—the abnormal enlargement of the heart—can lead to heart failure and death. Current therapies treat the symptoms of hypertrophy, but do not reverse tissue pathology. Thus, the development of strategies to restore cardiac function is a desirable goal. Previous work has suggested that treatment with growth differentiation factor II (GDFII) could be one such approach. However, while some studies indicate that raising GDFII levels in aged mice leads to rejuvenation of hypertrophic hearts and skeletal muscle, others purport that over-expression of GDF11 prompts cardiac and skeletal muscle wasting. In an attempt to resolve these disparate findings, Harper and colleagues performed a blinded dose-ranging study in which they treated both healthy mice and those with hypertrophy (from aortic constriction) for 2 weeks with daily doses of GDFII. They found that in mice with aortic constriction, high doses of GDFII reduced signs of hypertrophy, such as fibrosis, and improved pump function, but these doses were also associated with severe skeletal muscle wasting, weight loss and premature death in both groups. Such negative effects, the authors say, are likely to preclude clinical translation of GDFII-boosting treatments. Previous Back to top Next FiguresReferencesRelatedDetailsRelated articlesGDF11 Decreases Pressure Overload–Induced Hypertrophy, but Can Cause Severe Cachexia and Premature DeathShavonn C. Harper, et al. Circulation Research. 2018;123:1220-1231Macrophage Inflammation, Erythrophagocytosis, and Accelerated Atherosclerosis in Jak2V617F MiceWei Wang, et al. Circulation Research. 2018;123:e35-e47A Miniaturized, Programmable Pacemaker for Long-Term Studies in the MouseMaarten Hulsmans, et al. Circulation Research. 2018;123:1208-1219 November 9, 2018Vol 123, Issue 11 Advertisement Article InformationMetrics © 2018 American Heart Association, Inc.https://doi.org/10.1161/RES.0000000000000240PMID: 30571476 Originally publishedNovember 8, 2018 PDF download Advertisement