{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T05:31:15Z","timestamp":1792042275697,"version":"4.4.0"},"reference-count":55,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2019,6,28]],"date-time":"2019-06-28T00:00:00Z","timestamp":1561680000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000274","name":"BHF","doi-asserted-by":"publisher","award":["RG\/13\/7\/30099"],"award-info":[{"award-number":["RG\/13\/7\/30099"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000274","name":"BHF","doi-asserted-by":"publisher","award":["RE\/13\/5\/30177"],"award-info":[{"award-number":["RE\/13\/5\/30177"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"MRC","doi-asserted-by":"publisher","award":["76692\/1"],"award-info":[{"award-number":["76692\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"MRC","doi-asserted-by":"publisher","award":["MC_PC_14133"],"award-info":[{"award-number":["MC_PC_14133"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"name":"MRC Proximity to Discovery Award","award":["171319-06"],"award-info":[{"award-number":["171319-06"]}]},{"name":"BHF Chair award","award":["CH\/4\/29762"],"award-info":[{"award-number":["CH\/4\/29762"]}]},{"DOI":"10.13039\/501100004543","name":"China Scholarship Council","doi-asserted-by":"publisher","award":["201708060309"],"award-info":[{"award-number":["201708060309"]}],"id":[{"id":"10.13039\/501100004543","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Aims<\/jats:title>\n                  <jats:p>Transient Receptor Potential Melastatin 7 (TRPM7) cation channel is a chanzyme (channel + kinase) that influences cellular Mg2+ homeostasis and vascular signalling. However, the pathophysiological significance of TRPM7 in the cardiovascular system is unclear. The aim of this study was to investigate the role of this chanzyme in the cardiovascular system focusing on inflammation and fibrosis.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and results<\/jats:title>\n                  <jats:p>TRPM7-deficient mice with deletion of the kinase domain (TRPM7+\/\u0394kinase) were studied and molecular mechanisms investigated in TRPM7+\/\u0394kinase bone marrow-derived macrophages (BMDM) and co-culture systems with cardiac fibroblasts. TRPM7-deficient mice had significant cardiac hypertrophy, fibrosis, and inflammation. Cardiac collagen and fibronectin content, expression of pro-inflammatory mediators (SMAD3, TGF\u03b2) and cytokines [interleukin (IL)-6, IL-10, IL-12, tumour necrosis factor-\u03b1] and phosphorylation of the pro-inflammatory signalling molecule Stat1, were increased in TRPM7+\/\u0394kinase mice. These processes were associated with infiltration of inflammatory cells (F4\/80+CD206+ cardiac macrophages) and increased galectin-3 expression. Cardiac [Mg2+]i, but not [Ca2+]i, was reduced in TRPM7+\/\u0394kinase mice. Calpain, a downstream TRPM7 target, was upregulated (increased expression and activation) in TRPM7+\/\u0394kinase hearts. Vascular functional and inflammatory responses, assessed in vivo by intra-vital microscopy, demonstrated impaired neutrophil rolling, increased neutrophil: endothelial attachment and transmigration of leucocytes in TRPM7+\/\u0394kinase mice. TRPM7+\/\u0394kinase BMDMs had increased levels of galectin-3, IL-10, and IL-6. In co-culture systems, TRPM7+\/\u0394kinase macrophages increased expression of fibronectin, proliferating cell nuclear antigen, and TGF\u03b2 in cardiac fibroblasts from wild-type mice, effects ameliorated by MgCl2 treatment.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>We identify a novel anti-inflammatory and anti-fibrotic role for TRPM7 and suggest that its protective effects are mediated, in part, through Mg2+-sensitive processes.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/cvr\/cvz164","type":"journal-article","created":{"date-parts":[[2019,6,26]],"date-time":"2019-06-26T19:12:15Z","timestamp":1561576335000},"page":"721-735","source":"Crossref","is-referenced-by-count":106,"title":["Chanzyme TRPM7 protects against cardiovascular inflammation and fibrosis"],"prefix":"10.1093","volume":"116","author":[{"given":"Francisco J","family":"Rios","sequence":"first","affiliation":[{"name":"Institute of Cardiovascular and Medical Sciences, BHF Glasgow Cardiovascular Research Centre, University of Glasgow, 126 University Place, Glasgow G12 8TA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi-Guo","family":"Zou","sequence":"first","affiliation":[{"name":"Institute of Cardiovascular and Medical Sciences, BHF Glasgow Cardiovascular Research Centre, University of Glasgow, 126 University Place, Glasgow G12 8TA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2845-4982","authenticated-orcid":false,"given":"Adam P","family":"Harvey","sequence":"first","affiliation":[{"name":"Institute of Cardiovascular and Medical Sciences, BHF Glasgow Cardiovascular Research Centre, University of Glasgow, 126 University Place, Glasgow G12 8TA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katie Y","family":"Harvey","sequence":"first","affiliation":[{"name":"Institute of Cardiovascular and Medical Sciences, BHF Glasgow Cardiovascular Research Centre, University of Glasgow, 126 University Place, Glasgow G12 8TA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryszard","family":"Nosalski","sequence":"first","affiliation":[{"name":"Institute of Cardiovascular and Medical Sciences, BHF Glasgow Cardiovascular Research Centre, University of Glasgow, 126 University Place, Glasgow G12 8TA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Panagiota","family":"Anyfanti","sequence":"first","affiliation":[{"name":"3rd Department of Internal Medicine, Papageorgiou Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7451-7147","authenticated-orcid":false,"given":"Livia L","family":"Camargo","sequence":"first","affiliation":[{"name":"Institute of Cardiovascular and Medical Sciences, BHF Glasgow Cardiovascular Research Centre, University of Glasgow, 126 University Place, Glasgow G12 8TA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Lacchini","sequence":"first","affiliation":[{"name":"Department of Anatomy, Institute of Biomedical Sciences, University of S\u00e3o Paulo, S\u00e3o Paulo, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexey G","family":"Ryazanov","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lillia","family":"Ryazanova","sequence":"first","affiliation":[{"name":"Lewis Sigler Institute of Integrative Genomics, Princeton University, Princeton, NJ, 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