{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:50:56Z","timestamp":1792788656497,"version":"4.5.0"},"reference-count":56,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"10","funder":[{"name":"Deutsche Forschungsgemeinschaft","award":["AN372\/20-3"],"award-info":[{"award-number":["AN372\/20-3"]}],"id":[{"id":"https:\/\/ror.org\/018mejw64","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Deutsche Forschungsgemeinschaft","award":["TRR332 project A7"],"award-info":[{"award-number":["TRR332 project A7"]}],"id":[{"id":"https:\/\/ror.org\/018mejw64","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["JASN"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:sec>\n                    <jats:title>Key Points<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>Cholesterol crystal embolism causes arterial thrombosis, ischemic necrosis, and organ dysfunction.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Genetic depletion of cyclophilin D reduced cholesterol crystal embolism\u2013induced thromboinflammation and protected organ function.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Pharmacological inhibition of cyclophilin D and transmembrane protein 16F limited cholesterol crystal embolism\u2013induced thrombosis and improved kidney function.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Cholesterol crystal embolism is a severe consequence of advanced atherosclerosis, where intra-arterial cholesterol crystal can trigger organ injury and failure. Cyclophilin D (CypD), a key regulator of the mitochondrial permeability transition pore, promotes procoagulant platelet formation and necrosis. We hypothesized that CypD-dependent procoagulant platelet formation enhances cholesterol crystal embolism\u2013induced thromboinflammatory responses and kidney injury.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We used CypD-deficient mice and pharmacologic inhibitors (cyclosporine A to block CypD and niflumic acid to inhibit transmembrane protein 16F as a downstream effector of CypD) to determine the role of CypD during cholesterol crystal\u2013induced kidney thromboinflammation and injury.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Cholesterol crystal injection into the renal artery caused infarction, thromboinflammation, and AKI in wild-type mice, whereas CypD-deficient mice were protected. Global or platelet-specific CypD deletion preserved GFR, reduced infarct size, and attenuated tubular damage. Pharmacological inhibition of CypD with cyclosporin A conferred similar protection. Inhibition of transmembrane protein 16F-dependent phosphatidylserine exposure with niflumic acid also reduced CypD-mediated procoagulant activity and limited kidney injury.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our findings identified platelet CypD and downstream phosphatidylserine exposure as key mediators of cholesterol crystal\u2013induced thromboinflammation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1681\/asn.0000001088","type":"journal-article","created":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T16:01:02Z","timestamp":1775836862000},"page":"2103-2116","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":0,"title":["Platelet Cyclophilin D Drives Cholesterol Crystal Embolism\u2013Related Acute Kidney Injury and Kidney Infarction"],"prefix":"10.1681","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0683-4159","authenticated-orcid":false,"given":"Cong","family":"Li","sequence":"first","affiliation":[{"name":"Division of Nephrology, Department of Medicine IV, Ludwig Maximilian University Hospital, Munich, Germany"},{"name":"Department of Urology, Huai-An First People's Hospital Affiliated to Nanjing Medical University, Huaian, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-6232-0151","authenticated-orcid":false,"given":"Luying","family":"Yang","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine IV, Ludwig Maximilian University Hospital, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-4600-263X","authenticated-orcid":false,"given":"John","family":"Ku","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine IV, Ludwig Maximilian University Hospital, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9921-4284","authenticated-orcid":false,"given":"Peter","family":"Boor","sequence":"additional","affiliation":[{"name":"Institute of Pathology, University Clinic Aachen, RWTH Aachen University, Aachen, Germany"},{"name":"Electron Microscopy Facility, University Clinic Aachen, RWTH Aachen University, Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Zu","sequence":"additional","affiliation":[{"name":"Department of Urology, Huai-An First People's Hospital Affiliated to Nanjing Medical University, Huaian, China"},{"name":"Center for Neuropathology, Ludwig Maximilian University Hospital, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2537-2196","authenticated-orcid":false,"given":"Chao","family":"Han","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine IV, Ludwig Maximilian University Hospital, Munich, Germany"},{"name":"Walther Straub Institute of Pharmacology and Toxicology, Ludwig Maximilian University, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4675-6909","authenticated-orcid":false,"given":"Meisi","family":"Kuang","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine IV, Ludwig Maximilian University Hospital, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ye","family":"Fei","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine IV, Ludwig Maximilian University Hospital, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuyao","family":"Liu","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine IV, Ludwig Maximilian University Hospital, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Long","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine IV, Ludwig Maximilian University Hospital, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiubo","family":"Li","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine IV, Ludwig Maximilian University Hospital, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-3439-3096","authenticated-orcid":false,"given":"Liang","family":"Chang","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine IV, Ludwig Maximilian University Hospital, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9581-0548","authenticated-orcid":false,"given":"Huan","family":"Yang","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine IV, Ludwig Maximilian University Hospital, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-8532-6127","authenticated-orcid":false,"given":"Xiang","family":"Chu","sequence":"additional","affiliation":[{"name":"Walther Straub Institute of Pharmacology and Toxicology, Ludwig Maximilian University, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-8634-1852","authenticated-orcid":false,"given":"Heydar","family":"Aghakishi","sequence":"additional","affiliation":[{"name":"Walther Straub Institute of Pharmacology and Toxicology, Ludwig Maximilian University, 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