The Mast Cell

HomeArteriosclerosis, Thrombosis, and Vascular BiologyVol. 41, No. 4The Mast Cell Free AccessEditorialPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyRedditDiggEmail Jump toFree AccessEditorialPDF/EPUBThe CellA Novel Actor in Cardiac Microvessel Dysfunction Ilze Bot BotIlze Correspondence to: Bot, PhD, Einsteinweg 55, 2333 CC, Leiden, the Netherlands. Email E-mail Address: [email protected] https://orcid.org/0000-0002-1242-1959 Division of BioTherapeutics, Leiden Academic Centre for Drug Research, University, Search more papers by this author Originally published24 Mar 2021https://doi.org/10.1161/ATVBAHA.121.316043Arteriosclerosis, Biology. 2021;41:1337–1338This article is a commentary on followingMast Cells Are Trigger Small Vessel Disease Diastolic Diabetic Obese MiceIn last decade, mast cell, potent immune cell mainly known its function host defense responses contribution allergies, has gained attention as effector cardiovascular metabolic diseases such atherosclerosis, vein graft disease, diabetes, obesity.1 cells have been reported contribute underlying proinflammatory pathways involved these diseases, but can also directly affect surrounding tissue release proteases growth factors.See accompanying page e193In recent study Guimbal et al2 entitled “Mast Mice,” are now identified causal player cardiac microvessel disease leptin-receptor deficient (Leprdb/db) mice, an experimental model diastolic dysfunction associated with heart failure preserved ejection fraction. After confirming presence mouse model, authors show via RNA sequencing analysis extensive inflammation heart, prominent upregulation cell-related genes. Indeed, hearts Leprdb/db activated content was increased compared control mice. Being most activation mechanism, IgE-FcεRI (Fc epsilon receptor 1) pathway suggested be involved, despite elevated circulating IgE levels percentage that had bound their surface did not differ between groups. Although may suggest other mechanisms, complement receptors at play here, should excluded yet based binding only. FcεRI only sensitizes whereas antigen molecules results degranulation.3 Detailed fraction respect status IgE-antigen will provide evidence regarding disease. In addition, elucidation led striking increase mice mechanistic insights. For example, B-cell numbers shown point towards antibody-producing B upon dysfunction. Further characterization subsets thus valuable information processes This relevant given fact role IgE-FcεR1 established.4 models used Zhao al4 comparable dysfunction, were induction well, interestingly, blocking reduced remodeling vivo. depletion FcεR1 improved cardiomyocyte fibroblast vitro, suggesting antibodies direct effects nonmyeloid thereby contributing function.Nonetheless, compelling or specifically cell–derived histamine, contributes showing both stabilization cromolyn blockade H1 H1-antagonist cetirizine reduce diameter while reducing vascular leakage. Total vessel density treatment groups, functionality, growth, primarily affected heart. Similar findings earlier hypoxia, which local ischemic hindlimb enhanced collateral diameter, number.5 Also human advanced intraplaque microvessels prone become leaky hemorrhage.6 Together, studies demonstrate cells, when activated, severe impact different processes.Interestingly, inflammatory response number CD45+ tissue, suggests histamine predominant mediator responsible observed effects. However, secrete can, depending stimulus, cell–specific proteases, chymase tryptase, leukotrienes, vast amount cytokines enhance response. Release likely evident from inflammation. Therapeutically, it beneficial intervene rather than single mediator. Systemic however drawbacks do against pathogens. Therefore, any implicated, importance elucidate whether disease-specific trigger exists assess therapeutically targeted. Yet, study, antagonism appear promising therapeutic strategy vivo, rendering validation patients suffering warranted.Disclosures I. Established Investigator Dutch Heart Foundation (2019T067).FootnotesFor Disclosures, see 1338.The opinions expressed necessarily those editors American Association.Correspondence i.[email protected]leidenuniv.nlReferences1. Shi GP, I, Kovanen PT. cardiometabolic diseases.Nat Rev Cardiol. 2015; 12:643–658. doi: 10.1038/nrcardio.2015.117CrossrefMedlineGoogle Scholar2. S, Cornuault L, Rouault P, Hollier P-L, Chapouly C, Bats M-L, Imbault J, Gadeau A-P, Couffinhal T, Renault M-A. small diabetic obese mice.Arterioscler Thromb Vasc Biol. 2021; 41:e193––e207. 10.1161/ATVBAHA.121.315900LinkGoogle Scholar3. Galli SJ, Borregaard N, Wynn TA. Phenotypic functional plasticity innate immunity: macrophages, neutrophils.Nat Immunol. 2011; 12:1035–1044. 10.1038/ni.2109CrossrefMedlineGoogle Scholar4. H, Yang Geng Chen Y, Pang Shu M, Tang Li Z, B, al.. Role IgE-FcepsilonR1 pathological dysfunction.Circulation. 2020. 10.1161/CIRCULATIONAHA.120.047852Google Scholar5. Velden DV, Bouwman Kröner MJ, Kuiper Quax PHA, de Vries MR. Local promotes neovascularization.Cells. 2020; 9:701. 10.3390/cells9030701CrossrefGoogle Scholar6. Willems Vink A, PH, Borst GJ, JP, van Weg SM, Moll FL, PT, carotid atherosclerotic plaques occurrence future events.Eur J. 2013; 34:3699–3706. 10.1093/eurheartj/eht186CrossrefMedlineGoogle Scholar Previous Back top Next FiguresReferencesRelatedDetailsRelated articlesMast MiceSarah Guimbal, al. Arteriosclerosis, 2021;41:e193-e207 April 2021Vol Issue 4Article InformationMetrics Download: 96 © 2021 Association, Inc.https://doi.org/10.1161/ATVBAHA.121.316043PMID: 33760636 publishedMarch 24, Keywordsmast cellEditorialsinflammationmicrovesselatherosclerosisheart failurePDF download