In This Issue

Abstract

HomeCirculation ResearchVol. 125, No. 1In 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 published20 Jun 2019https://doi.org/10.1161/RES.0000000000000281Circulation Research. 2019;125:2is related toRelationship Between Serum Alpha-Tocopherol and Overall and Cause-Specific Mortalityis related toMitochondria Are a Subset of Extracellular Vesicles Released by Activated Monocytes and Induce Type I IFN and TNF Responses in Endothelial CellsMacrophage Smad3 Protects the Infarcted Heart, Stimulating Phagocytosis and Regulating InflammationSerum Alpha-Tocopherol and Mortality (p 29)A 30-year study suggests vitamin E has long-term health benefits, say Huang et al.Vitamin E, or α-tocopherol, is an essential fat-soluble vitamin acquired via consumption of vegetable oils, nuts, seeds, whole grains, and certain fruits and vegetables. With reported antioxidant, anti-inflammatory, and tumor-suppressive activities, α-tocopherol has apparent health benefits. But, while a lower risk of all-cause mortality has been linked to higher α-tocopherol levels in people, studies show inconsistent links with cause-specific deaths, such as those from cancer and cardiovascular disease. To look more closely at cause-specific mortality, Huang and colleagues have studied a cohort of almost 30,000 Finnish men who were in their 50s and 60s at the start of a 30-year health study and who had α-tocopherol levels, among other metrics, measured at baseline. From ≈24,000 deaths, and after adjusting for age and major risk factors such as smoking, the team found that α-tocopherol levels were inversely associated with the risk of death from cardiovascular disease, heart disease, stroke, cancer, respiratory disease, other-causes and all-causes, but not with risk of death from diabetes or injuries and accidents. The authors say these results indicate vitamin E may influence longevity, but also highlight the need for further studies in ethnically diverse populations and women.Stressed Mitochondria Activate Endothelial Cells (p 43)Download figureDownload PowerPointMitochondria released from activated monocytes are proinflammatory, report Puhm et al.Extracellular vesicles, such as microvesicles (MVs), are small, membrane-bound packages released from cells that enable cell-to-cell communication. While these vesicles can be released under normal conditions, their abundance, contents, and origin may alter with, and even influence, disease states. MVs released from monocytes after bacterial LPS stimulation, for example, have been shown to contain abundant mitochondrial proteins. Mitochondrial DNA-containing MVs have also been reported in a mouse model of inflammation. Puhm and colleagues, therefore, hypothesized that the mitochondrial content of MVs might actively contribute to proinflammatory effects. The team found that LPS-stimulated monocytes not only release mitochondria-containing MVs but also free mitochondria themselves. These free and MV-encapsulated mitochondria were shown to induce endothelial cells to produce the inflammatory cytokines TNFα and interferon. Circulating MVs collected from LPS-injected human volunteers also prompted such endothelial cytokine production. Furthermore, inhibition of mitochondrial activity drastically reduced this proinflammatory capacity of monocyte-released MVs. Together, the results indicate that released mitochondria, whether free or in MVs, may be key players in certain inflammatory diseases.Macrophage Smad3 in Myocardial Infarction (p 55)Download figureDownload PowerPointSmad3 in heart macrophages protects against excess infarct damage, say Chen et al.After an injury, increased local levels of cytokine TGF-β can, depending on conditions, stimulate macrophages to adopt either proinflammatory or anti-inflammatory phenotypes, both of which involve activation of signal transducer Smad3. Since inflammation can influence the outcome of injuries, including myocardial infarctions, Chen and colleagues investigated the overall impact of the TGF-β/Smad3 pathway in postinfarction macrophages. The team found that mice engineered to lack Smad3 in macrophages faired poorly following infarction. Survival was reduced compared with control mice and the animals’ hearts exhibited increased adverse remodeling and greater impairment of function. The Smad3-lacking cells themselves showed perturbed phagocytic activity, sustained expression of proinflammatory genes, and reduced production of anti-inflammatory mediators when compared with control macrophages. These results suggest Smad3 is necessary for postinfarction macrophages to transition to an anti-inflammatory, phagocytic phenotype that protects against excess remodeling. Smad3 inhibition in cardiomyocytes has been reported to be protective against infarction damage, however. So, any potential Smad3-modifying therapies would require cell-type–specific deployment, say the authors. Previous Back to top Next FiguresReferencesRelatedDetailsRelated articlesRelationship Between Serum Alpha-Tocopherol and Overall and Cause-Specific MortalityJiaqi Huang, et al. Circulation Research. 2019;125:29-40Mitochondria Are a Subset of Extracellular Vesicles Released by Activated Monocytes and Induce Type I IFN and TNF Responses in Endothelial CellsFlorian Puhm, et al. Circulation Research. 2019;125:43-52Macrophage Smad3 Protects the Infarcted Heart, Stimulating Phagocytosis and Regulating InflammationBijun Chen, et al. Circulation Research. 2019;125:55-70 June 21, 2019Vol 125, Issue 1 Advertisement Article InformationMetrics © 2019 American Heart Association, Inc.https://doi.org/10.1161/RES.0000000000000281 Originally publishedJune 20, 2019 PDF download Advertisement