{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T19:00:37Z","timestamp":1784746837088,"version":"3.55.0"},"reference-count":62,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"8","license":[{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>Local and systemic endothelial dysfunction following traumatic brain injury (TBI) results in secondary cerebral and pulmonary edema, tissue ischemia, and inflammation. However, the underlying mechanism of the endothelial dysfunction beyond the site of the primary trauma remains poorly understood. Morphologically intact and metabolically active extracellular mitochondria (exMt) accounted for 55.2% of brain-derived extracellular vesicles found in the peripheral blood of mice subjected to severe TBI. This observation led us to investigate the role of exMt in TBI-induced secondary endothelial injury.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>We measured circulating exMt in patients with TBI and mice subjected to TBI and examined the effects of exMt on endothelial cells in vitro and in vivo. Mechanistic studies involved evaluating Cavin-1-dependent endocytosis of exMt and its downstream effects on endothelial cells, including mitophagy activation, lysosomal dysfunction, and apoptosis. The findings were validated in Cavin-1 knockdown endothelial cells and Cavin-1-deficient mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>Here, we report the detection of high levels of exMt in the peripheral blood samples from patients with TBI. These circulating exMt bound to and were endocytosed by endothelial cells via a Cavin-1-dependent pathway. exMt activated endothelial cells, caused vascular leakage, and promoted an inflammatory response in vitro. Furthermore, noninjured mice infused with exMt developed similar changes in the brain and lungs. exMt endocytosed by endothelial cells activated mitophagy and promoted the formation of mitophagosomes but impaired lysosomal function, leading to endothelial cell apoptosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>Results from this study demonstrate a novel subcellular mechanism for exMt-induced endothelial dysfunction during acute TBI.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/atvbaha.126.323502","type":"journal-article","created":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T09:00:38Z","timestamp":1782378038000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["Extracellular Mitochondria Mediate Endothelial Injury After Traumatic Brain Injury"],"prefix":"10.1161","volume":"46","author":[{"given":"Lujia","family":"Tang","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, State Key Laboratory of Experimental Hematology, Tianjin Neurological Institute (L.T., Y. Liu, K.P., Y.Z., X.Z., P.Z., Z. Zhou, H.Z., T.M., J.Z., Z. Zhao), Tianjin Medical University General Hospital, China."},{"name":"Huanhu Hospital Affiliated to Tianjin Medical University, Tianjin Medical University, China (L.T., M.W.)."},{"name":"Department of Neurosurgery, Tianjin Key Laboratory of Cerebral Vascular and Neurodegenerative Diseases, Tianjin Huanhu Hospital, China (L.T., M.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4200-0098","authenticated-orcid":true,"given":"Yafan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, State Key Laboratory of Experimental Hematology, Tianjin Neurological Institute (L.T., Y. Liu, K.P., Y.Z., X.Z., P.Z., Z. Zhou, H.Z., T.M., J.Z., Z. Zhao), Tianjin Medical University General Hospital, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaifeng","family":"Pang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, State Key Laboratory of Experimental Hematology, Tianjin Neurological Institute (L.T., Y. Liu, K.P., Y.Z., X.Z., P.Z., Z. Zhou, H.Z., T.M., J.Z., Z. Zhao), Tianjin Medical University General Hospital, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Li","sequence":"additional","affiliation":[{"name":"Precision Medicine Center (Y. Li), Tianjin Medical University General Hospital, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-2735-8626","authenticated-orcid":true,"given":"Yichi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, State Key Laboratory of Experimental Hematology, Tianjin Neurological Institute (L.T., Y. Liu, K.P., Y.Z., X.Z., P.Z., Z. Zhou, H.Z., T.M., J.Z., Z. Zhao), Tianjin Medical University General Hospital, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5494-589X","authenticated-orcid":true,"given":"Xiaoxi","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology &amp; Oncology and Key Laboratory of Birth Defects and Related Diseases of Women and Children, West China Second Hospital, Sichuan University School of Medicine, Chengdu (X.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, State Key Laboratory of Experimental Hematology, Tianjin Neurological Institute (L.T., Y. Liu, K.P., Y.Z., X.Z., P.Z., Z. Zhou, H.Z., T.M., J.Z., Z. Zhao), Tianjin Medical University General Hospital, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengbo","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, State Key Laboratory of Experimental Hematology, Tianjin Neurological Institute (L.T., Y. Liu, K.P., Y.Z., X.Z., P.Z., Z. Zhou, H.Z., T.M., J.Z., Z. Zhao), Tianjin Medical University General Hospital, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zijian","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, State Key Laboratory of Experimental Hematology, Tianjin Neurological Institute (L.T., Y. Liu, K.P., Y.Z., X.Z., P.Z., Z. Zhou, H.Z., T.M., J.Z., Z. 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