{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T01:45:12Z","timestamp":1793065512369,"version":"4.5.0"},"reference-count":54,"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":[[2016,8]]},"abstract":"<jats:sec>\n            <jats:title>Objective\u2014<\/jats:title>\n            <jats:p>\n              Activation of platelets by subendothelial collagen results in an increase of cytosolic Ca\n              <jats:sup>2+<\/jats:sup>\n              concentration ([Ca\n              <jats:sup>2+<\/jats:sup>\n              ]\n              <jats:sub>i<\/jats:sub>\n              ) and is followed by platelet activation and thrombus formation that may lead to vascular occlusion. The present study determined the role of phosphoinositide-dependent protein kinase 1 (PDK1) in collagen-dependent platelet Ca\n              <jats:sup>2+<\/jats:sup>\n              signaling and ischemic stroke in vivo.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results\u2014<\/jats:title>\n            <jats:p>\n              Platelet activation with collagen receptor glycoprotein VI agonists collagen-related peptide or convulxin resulted in a significant increase in PDK1 activity independent of second-wave signaling. PDK1 deficiency was associated with reduced platelet phospholipase C\u03b32\u2013dependent inositol-1,4,5-trisphosphate production and intracellular [Ca\n              <jats:sup>2+<\/jats:sup>\n              ]\n              <jats:sub>i<\/jats:sub>\n              in response to stimulation with collagen-related peptide or convulxin. The defective increase of [Ca\n              <jats:sup>2+<\/jats:sup>\n              ]\n              <jats:sub>i<\/jats:sub>\n              resulted in a substantial defect in activation-dependent platelet secretion and aggregation on collagen-related peptide stimulation. Furthermore, Rac1 activation and spreading, adhesion to collagen, and thrombus formation under high arterial shear rates were significantly diminished in PDK1-deficient platelets. Mice with PDK1-deficient platelets were protected against arterial thrombotic occlusion after FeCl\n              <jats:sub>3<\/jats:sub>\n              -induced mesenteric arterioles injury and ischemic stroke in vivo. These mice had significantly reduced brain infarct volumes, with a significantly increased survival of 7 days after transient middle cerebral artery occlusion without increase of intracerebral hemorrhage. Tail bleeding time was prolonged in\n              <jats:italic>pdk1<\/jats:italic>\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              mice, reflecting an important role of PDK1 in primary hemostasis.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>\n              PDK1 is required for Ca\n              <jats:sup>2+<\/jats:sup>\n              -dependent platelet activation on stimulation of collagen receptor glycoprotein VI, arterial thrombotic occlusion, and ischemic stroke in vivo.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/atvbaha.115.307105","type":"journal-article","created":{"date-parts":[[2016,6,24]],"date-time":"2016-06-24T03:04:14Z","timestamp":1466737454000},"page":"1507-1516","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":33,"title":["PDK1 Determines Collagen-Dependent Platelet Ca\n            <sup>2+<\/sup>\n            Signaling and Is Critical to Development of Ischemic Stroke In Vivo"],"prefix":"10.1161","volume":"36","author":[{"given":"Patrick","family":"M\u00fcnzer","sequence":"first","affiliation":[{"name":"From the Department of Cardiology and Cardiovascular Medicine (P.M., B.W.-A., S.G., D.R., D.E., T.G., M.G., O.B.), Department of Physiology (B.W.-A., F.L.), Department of Evolutionary Biology of Invertebrates, Institute for Evolution and Ecology (M.M.), Department of Dermatology (M.S.), and Department of Clinical Pharmacology (M.S.), University of T\u00fcbingen, T\u00fcbingen, Germany; Department of Neurology, University of W\u00fcrzburg, W\u00fcrzburg, Germany (E.G., C.K.); Institute for Immunology and Transfusion..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Britta","family":"Walker-Allgaier","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology and Cardiovascular Medicine (P.M., B.W.-A., S.G., D.R., D.E., T.G., M.G., O.B.), Department of Physiology (B.W.-A., F.L.), Department of Evolutionary Biology of Invertebrates, Institute for Evolution and Ecology (M.M.), Department of Dermatology (M.S.), and Department of Clinical Pharmacology (M.S.), University of T\u00fcbingen, T\u00fcbingen, Germany; Department of Neurology, University of W\u00fcrzburg, W\u00fcrzburg, Germany (E.G., C.K.); Institute for Immunology and Transfusion..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sascha","family":"Geue","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology and Cardiovascular Medicine (P.M., B.W.-A., S.G., D.R., D.E., T.G., M.G., O.B.), Department of Physiology (B.W.-A., F.L.), Department of Evolutionary Biology of Invertebrates, Institute for Evolution and Ecology (M.M.), Department of Dermatology (M.S.), and Department of Clinical Pharmacology (M.S.), University of T\u00fcbingen, T\u00fcbingen, Germany; Department of Neurology, University of W\u00fcrzburg, W\u00fcrzburg, Germany (E.G., C.K.); Institute for Immunology and Transfusion..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Geuss","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology and Cardiovascular Medicine (P.M., B.W.-A., S.G., D.R., D.E., T.G., M.G., O.B.), Department of Physiology (B.W.-A., F.L.), Department of Evolutionary Biology of Invertebrates, Institute for Evolution and Ecology (M.M.), Department of Dermatology (M.S.), and Department of Clinical Pharmacology (M.S.), University of T\u00fcbingen, T\u00fcbingen, Germany; Department of Neurology, University of W\u00fcrzburg, W\u00fcrzburg, Germany (E.G., C.K.); Institute for Immunology and Transfusion..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregor","family":"Hron","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology and Cardiovascular Medicine (P.M., B.W.-A., S.G., D.R., D.E., T.G., M.G., O.B.), Department of Physiology (B.W.-A., F.L.), Department of Evolutionary Biology of Invertebrates, Institute for Evolution and Ecology (M.M.), Department of Dermatology (M.S.), and Department of Clinical Pharmacology (M.S.), University of T\u00fcbingen, T\u00fcbingen, Germany; Department of Neurology, University of W\u00fcrzburg, W\u00fcrzburg, Germany (E.G., C.K.); Institute for Immunology and Transfusion..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominik","family":"Rath","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology and Cardiovascular Medicine (P.M., B.W.-A., S.G., D.R., D.E., T.G., M.G., O.B.), Department of Physiology (B.W.-A., F.L.), Department of Evolutionary Biology of Invertebrates, Institute for Evolution and Ecology (M.M.), Department of Dermatology (M.S.), and Department of Clinical Pharmacology (M.S.), University of T\u00fcbingen, T\u00fcbingen, Germany; Department of Neurology, University of 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