{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T11:46:36Z","timestamp":1791978396643,"version":"4.4.0"},"reference-count":62,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"8","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2023,8]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>MAGT1 (magnesium transporter 1) is a subunit of the oligosaccharide protein complex with thiol-disulfide oxidoreductase activity, supporting the process of N-glycosylation. MAGT1 deficiency was detected in human patients with X-linked immunodeficiency with magnesium defect syndrome and congenital disorders of glycosylation, resulting in decreased cation responses in lymphocytes, thereby inhibiting the immune response against viral infections. Curative hematopoietic stem cell transplantation of patients with X-linked immunodeficiency with magnesium defect causes fatal bleeding and thrombotic complications.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>We studied the role of MAGT1 deficiency in platelet function in relation to arterial thrombosis and hemostasis using several in vitro experimental settings and in vivo models of arterial thrombosis and transient middle cerebral artery occlusion model of ischemic stroke.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>\n                      MAGT1-deficient mice (\n                      <jats:italic toggle=\"yes\">\n                        Magt1\n                        <jats:sup>\u2212\/y<\/jats:sup>\n                      <\/jats:italic>\n                      ) displayed accelerated occlusive arterial thrombus formation in vivo, a shortened bleeding time, and profound brain damage upon focal cerebral ischemia. These defects resulted in increased calcium influx and enhanced second wave mediator release, which further reinforced platelet reactivity and aggregation responses. Supplementation of MgCl\n                      <jats:sub>2<\/jats:sub>\n                      or pharmacological blockade of TRPC6 (transient receptor potential cation channel, subfamily C, member 6) channel, but not inhibition of store-operated calcium entry, normalized the aggregation responses of\n                      <jats:italic toggle=\"yes\">\n                        Magt1\n                        <jats:sup>\u2212\/y<\/jats:sup>\n                      <\/jats:italic>\n                      platelets to the control level. GP (glycoprotein) VI activation of\n                      <jats:italic toggle=\"yes\">\n                        Magt1\n                        <jats:sup>\u2212\/y<\/jats:sup>\n                      <\/jats:italic>\n                      platelets resulted in hyperphosphorylation of Syk (spleen tyrosine kinase), LAT (linker for activation of T cells), and PLC (phospholipase C) \u03b32, whereas the inhibitory loop regulated by PKC (protein kinase C) was impaired. A hyperaggregation response to the GPVI agonist was confirmed in human platelets isolated from a MAGT1-deficient (X-linked immunodeficiency with magnesium defect) patient. Haploinsufficiency of TRPC6 in\n                      <jats:italic toggle=\"yes\">\n                        Magt1\n                        <jats:sup>\u2212\/y<\/jats:sup>\n                      <\/jats:italic>\n                      mice could normalize GPVI signaling, platelet aggregation, and thrombus formation in vivo.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>These results suggest that MAGT1 and TRPC6 are functionally linked. Therefore, deficiency or impaired functionality of MAGT1 could be a potential risk factor for arterial thrombosis and stroke.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/atvbaha.122.318115","type":"journal-article","created":{"date-parts":[[2023,6,29]],"date-time":"2023-06-29T05:00:24Z","timestamp":1688014824000},"page":"1494-1509","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":15,"title":["MAGT1 Deficiency Dysregulates Platelet Cation Homeostasis and Accelerates Arterial Thrombosis and Ischemic Stroke in Mice"],"prefix":"10.1161","volume":"43","author":[{"given":"Sanjeev Kiran","family":"Gotru","sequence":"first","affiliation":[{"name":"Institute of Experimental Biomedicine, University Hospital and Rudolf Virchow Center (S.K.G., K.S., S.B., S.S., B.N., A.B.), University of W\u00fcrzburg, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elmina","family":"Mammadova-Bach","sequence":"additional","affiliation":[{"name":"Walther Straub Institute of Pharmacology and Toxicology, Faculty of Medicine, Ludwig-Maximilians University, Munich, Germany (E.M.-B., M.M., A.P., C.H., A.D., T.G., A.B.)."},{"name":"Division of Nephrology, Department of Medicine IV, Ludwig-Maximilians University Hospital, Munich, Germany (E.M.-B., M.M., C.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0855-2945","authenticated-orcid":true,"given":"Georgios","family":"Sogkas","sequence":"additional","affiliation":[{"name":"Cluster of Excellence RESIST (G. 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