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HomeCirculation ResearchVol. 131, No. 2In 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 published7 Jul 2022https://doi.org/10.1161/RES.0000000000000560Circulation Research. 2022;131:127is related toBrown Adipocyte ADRB3 Mediates Cardioprotection via Suppressing Exosomal iNOSPiezo1-Regulated Mechanotransduction Controls Flow-Activated Lymphatic ExpansionInterleukin-6 Predicts Carotid Plaque Severity, Vulnerability, and ProgressionPiezo1-Regulated Mechanotransduction Controls Flow-Activated Lymphatic Expansion (p e2)Piezo activation drives growth of the lymphatic network, report Choi et al.Download figureDownload PowerPointAs well as being thoroughfares for immune cells, lymph vessels are drainage channels that help maintain tissue fluid homeostasis. This network of branching tubes grows as fluids begin to flow in the developing embryo. Indeed, fluid flow induces calcium influx into lymphatic endothelial cells (LECs), which in turn promotes proliferation and migration of the cells and, ultimately, sprouting of lymph tubules. But how do LECs detect fluid flow in the first place? Piezo1 is a flow-sensing mechanosensory protein known for its role in blood vessel development and, furthermore, certain mutations to Piezo1 cause abnormal lymphatic growth in humans. Choi and colleagues now show that Piezo1 is expressed in embryonic mouse LECs and that suppression of Piezo1 inhibits both flow-activated calcium entry (via the channel Orai1) and downstream target gene activation. Overexpression of Piezo1, by contrast, induced the target genes. The team went on to show that mice lacking either Piezo1 or Orai1 had lymphatic sprouting defects, and that pharmacological activation of Piezo1 in mice enhanced lymphangiogenesis and prevented edema after tail surgery. Together the results confirm Piezo1’s role in flow-dependent lymphatic growth and suggest it might be a target for treating lymphedema.Brown Adipocyte ADRB3 Mediates Cardioprotection via Suppressing Exosomal iNOS (p 133)Activation of ADRB3 in brown fat protects the heart from fibrosis, report Lin et al.Download figureDownload PowerPointWhile overactivation of β1 and β2 adrenergic receptors can lead to heart damage, the same is not true for the third subtype—ADRB3. Activation of this receptor, which is primarily expressed in brown adipose tissue (BAT), is linked to beneficial metabolic activity and heart protection. And, as Lin and colleagues now show, this is not the only way ADRB3 protects the heart. The team studied mice with a BAT-specific deletion of ADRB3 and found, after a month of angiotensin II (Ang II)-induced hypertension, that the animals fared worse than controls (suffering exacerbated cardiac hypertrophy and fibrosis). In vitro experiments indicated this negative fibrotic effect of ADRB3 deletion was due, at least in part, to direct communication between the adipocytes and heart cells, specifically via adipocyte-released exosomes containing induced nitric oxide synthase (iNOS)—an enzyme previously implicated in cardiac dysfunction. The authors surmised that ADRB3 normally suppresses iNOS to protect the heart and showed that while exosomes with high iNOS exacerbated Ang-II-induced heart damage when infused into mice, silencing iNOS prevented this. The work thus highlights a novel BAT-to-heart communication system and identifies factors involved that could be clinically targeted to tackle heart disease.Interleukin-6 Predicts Carotid Plaque Severity, Vulnerability and Progression (p e22)Plasma levels of IL-6 predict stroke risk from carotid artery disease, say Kamtchum-Tatuene et al.Download figureDownload PowerPointExcessive plasma cholesterol together with systemic inflammation are contributing factors in atherosclerosis. While traditional remedies have been aimed at lowering a patient’s lipid levels, drugs that tackle inflammation are now also under investigation, including those that suppress interleukin-6 (IL-6)—an inflammatory cytokine implicated in the disease. Focusing on carotid artery disease—the presence of atherosclerotic plaques in major blood vessels supplying the brain—Kamtchum-Tatuene and colleagues investigated whether IL-6 levels correlated with disease severity. They examined levels of the cytokine and data from carotid artery ultrasounds—taken five years apart to assess the presence, severity and progression of plaques—for 4334 individuals enrolled in the Cardiovascular Health Study (CHS) cohort—an NIH-funded prospective population study. IL-6 was found to robustly correlate with and predict plaque severity independent of other cardiovascular risk factors. The study also determined a threshold IL-6 blood plasma level of 2.0pg/ml that identifies individuals with the highest likelihood of plaque vulnerability and progression. This threshold value, say the authors, could be used to select patients who might benefit from novel IL-6-lowering medications. Previous Back to top Next FiguresReferencesRelatedDetailsRelated articlesBrown Adipocyte ADRB3 Mediates Cardioprotection via Suppressing Exosomal iNOSJing-Rong Lin, et al. Circulation Research. 2022;131:133-147Piezo1-Regulated Mechanotransduction Controls Flow-Activated Lymphatic ExpansionDongwon Choi, et al. Circulation Research. 2022;131:e2-e21Interleukin-6 Predicts Carotid Plaque Severity, Vulnerability, and ProgressionJoseph Kamtchum-Tatuene, et al. Circulation Research. 2022;131:e22-e33 July 8, 2022Vol 131, Issue 2Article InformationMetrics © 2022 American Heart Association, Inc.https://doi.org/10.1161/RES.0000000000000560 Originally publishedJuly 7, 2022 PDF download Advertisement