HomeCirculationVol. 144, No. 16From the Literature Free AccessNewsPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessNewsPDF/EPUBFrom the Literature Tracy Hampton, PhD Tracy HamptonTracy Hampton Search for more papers by this author Originally published18 Oct 2021https://doi.org/10.1161/CIRCULATIONAHA.121.057430Circulation. 2021;144:1349–1350Erythropoietin Promotes Abdominal Aortic Aneurysms in MiceNew research indicates that erythropoietin (EPO) may help drive the formation of abdominal aortic aneurysm (AAA), a potentially fatal vascular disease characterized by localized dilation of the abdominal aorta. As reported in Science Translational Medicine, investigators found that EPO, a hormone secreted by the kidneys to increase red blood cell production in response to falling oxygen levels in tissues, promoted the formation of AAA in a dose-dependent manner in wild-type mice and in apolipoprotein E knockout (Apoe−/−) mice (a model for atherosclerosis). EPO monoclonal antibodies and EPO receptor knockdown in the mouse models reduced the incidence of AAA.EPO-induced AAA in mice exhibited pathological features similar to those of human AAA, including greater microvessel density, elevated angiogenesis, an increased inflammatory response, and reduced amounts of collagen and fewer smooth muscle cells. Experiments that investigated the mechanisms involved demonstrated that EPO induces proliferation, migration, and tube formation of endothelial cells via the JAK2/STAT5 signaling pathway.In humans, serum EPO concentrations were higher in patients with AAA than in healthy controls, and concentrations correlated with the size of the AAA.“If our preliminary findings are confirmed in future clinical studies in a large sample of patients with AAA, targeted therapy to reduce EPO levels in high-risk patients may be warranted,” said coauthor Dr Yun Zhang, of Shandong University Qilu Hospital, in China.The results also suggest that people with chronic hypoxia or those living at high altitudes should be screened for AAA, because these populations have elevated levels of EPO. Such surveillance might also benefit patients receiving long-term EPO treatment, such as individuals with kidney failure and severe anemia.Last, the research offers a new mouse model of AAA, one that involves administering high doses of EPO regardless of hyperlipidemia and hypertension status.Download figureDownload PowerPointResults from experiments involving mice and humans suggest that the hormone erythropoietin, whose structure is depicted here, may help drive the formation of abdominal aortic aneurysms.Zhang M et al. Erythropoietin promotes abdominal aortic aneurysms in mice through angiogenesis and inflammatory infiltration. Sci Transl Med. 2021;13:eaaz4959. doi: 10.1126/scitranslmed.aaz4959Molecular Imaging Provides Insights Into Inflammation and Fibrosis in Pressure Overload Heart FailureIn patients with heart disease, inflammation and subsequent fibrosis can contribute to the development of heart failure; however, the dynamic relationship between inflammation and fibrosis in nonischemic pressure overload–induced heart failure remains poorly characterized. In a study published in Circulation Research, investigators used medical imaging technologies to visualize these processes in the early response to pressure overload in a mouse model of transverse aortic constriction.“Specifically, we inject a radioactive probe that binds to white blood cells and tracks their distribution to define the local inflammation in the heart, and we combine this with MRI that detects changes in tissue density,” explained senior author Dr James Thackeray, of Hannover Medical School, in Germany. “In this study, we demonstrate the ability to see these molecular changes early in disease onset, which we can then use to predict the severity of disease progression.”The team’s imaging methods also quantitatively detected reduced levels of inflammation and fibrosis when elevated afterload was alleviated by mechanical unloading, which restored cardiac function.“These cellular changes are not the same for all failing hearts. Applying such imaging techniques early after symptom onset could identify specific patients with excessive immune response or fibrosis who might benefit from more targeted therapy,” said Dr Thackeray. “Also, for mechanical therapy such as left ventricular assist devices, imaging could give an early indication of the effectiveness of the therapy, particularly if a threshold of damage or molecular changes prevents the beneficial effect of ventricle unloading.”Glasenapp A et al. Molecular imaging of inflammation and fibrosis in pressure overload heart failure. Circ Res. 2021;129:369–382. doi: 10.1161/CIRCRESAHA.120.318539Long Noncoding RNA May Protect Against Heart Failure ProgressionMore than 99% of the human genome consists of sequences that do not code for proteins, with much of that genetic material being transcribed into long noncoding RNA. Now a team of investigators has identified a novel long noncoding RNA, Caren (short for cardiomyocyte-enriched noncoding transcript), that is expressed at high levels in cardiomyocytes.In a study published in Nature Communications, the researchers showed that Caren transcript levels were significantly lower in the hearts of aged mice relative to young mice and in a mouse model of heart failure. Also, after transverse aortic constriction, mice engineered to lack Caren were more vulnerable to pressure overload–induced cardiac dysfunction and heart failure–associated death than control mice. In contrast, overexpression of Caren protected mice against transverse aortic constriction–induced heart failure.In cardiac tissue of patients with heart failure, the amount of Caren was inversely correlated with the abundances of heart failure marker genes, so that patient tissue with high heart failure marker gene expression had low Caren RNA levels. Also, lowering Caren RNA levels in human inducible pluripotent stem cell–derived cardiomyocytes caused a decrease in the energy production capacity of mitochondria.Experiments revealed that Caren maintains cardiac function by inactivating the ataxia telangiectasia–mutated DNA damage response pathway and increases the number of mitochondria in cardiomyocytes to enhance energy production. Caren appears to exert its effects by suppressing the production of the tumor suppressor histidine triad nucleotide-binding protein 1.The findings suggest that increasing the amount of Caren RNA in cardiomyocytes may be a therapeutic strategy to inhibit the onset and progression of heart failure.Sato M et al. The lncRNA Caren antagonizes heart failure by inactivating DNA damage response and activating mitochondrial biogenesis. Nat Commun. 2021;12:2529. doi: 10.1038/s41467-021-22735-7Footnoteshttps://www.ahajournals.org/journal/circThe opinions expressed in this article are not necessarily those of the editors or of the American Heart Association. Previous Back to top Next FiguresReferencesRelatedDetails October 19, 2021Vol 144, Issue 16 Advertisement Article InformationMetrics © 2021 American Heart Association, Inc.https://doi.org/10.1161/CIRCULATIONAHA.121.057430 Originally publishedOctober 18, 2021 PDF download Advertisement