{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T06:37:20Z","timestamp":1787726240642,"version":"build-2784847793"},"reference-count":50,"publisher":"American Society for Clinical Investigation","issue":"10","license":[{"start":{"date-parts":[[2023,5,22]],"date-time":"2023-05-22T00:00:00Z","timestamp":1684713600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000050","name":"NHLBI","doi-asserted-by":"crossref","award":["National Institutes of Health grant RO1HL077328 (IP)"],"award-info":[{"award-number":["National Institutes of Health grant RO1HL077328 (IP)"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000050","name":"NHLBI","doi-asserted-by":"crossref","award":["National Institutes of Health grant R35-HL140039-03S1 (WJ)."],"award-info":[{"award-number":["National Institutes of Health grant R35-HL140039-03S1 (WJ)."]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100012308","name":"National Jewish Health","doi-asserted-by":"crossref","award":["Wollowick Chair of Pulmonary Research,National Jewish Health (IP);"],"award-info":[{"award-number":["Wollowick Chair of Pulmonary Research,National Jewish Health (IP);"]}],"id":[{"id":"10.13039\/100012308","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,5,22]]},"abstract":"<jats:p>The pathogenesis of the marked pulmonary microvasculature injury, a distinguishing feature of COVID-19 acute respiratory distress syndrome (COVID-ARDS), remains unclear. Implicated in the pathophysiology of diverse diseases characterized by endothelial damage, including ARDS and ischemic cardiovascular disease, ceramide and in particular palmitoyl ceramide (C16:0-ceramide) may be involved in the microvascular injury in COVID-19. Using deidentified plasma and lung samples from COVID-19 patients, ceramide profiling by mass spectrometry was performed. Compared with healthy individuals, a specific 3-fold C16:0-ceramide elevation in COVID-19 patient plasma was identified. Compared with age-matched controls, autopsied lungs of individuals succumbing to COVID-ARDS displayed a massive 9-fold C16:0-ceramide elevation and exhibited a previously unrecognized microvascular ceramide-staining pattern and markedly enhanced apoptosis. In COVID-19 plasma and lungs, the C16-ceramide\/C24-ceramide ratios were increased and reversed, respectively, consistent with increased risk of vascular injury. Indeed, exposure of primary human lung microvascular endothelial cell monolayers to C16:0-ceramide\u2013rich plasma lipid extracts from COVID-19, but not healthy, individuals led to a significant decrease in endothelial barrier function. This effect was phenocopied by spiking healthy plasma lipid extracts with synthetic C16:0-ceramide and was inhibited by treatment with ceramide-neutralizing monoclonal antibody or single-chain variable fragment. These results indicate that C16:0-ceramide may be implicated in the vascular injury associated with COVID-19.<\/jats:p>","DOI":"10.1172\/jci.insight.156104","type":"journal-article","created":{"date-parts":[[2023,5,21]],"date-time":"2023-05-21T14:00:56Z","timestamp":1684677656000},"source":"Crossref","is-referenced-by-count":22,"title":["Marked elevations in lung and plasma ceramide in COVID-19 linked to microvascular injury"],"prefix":"10.1172","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1094-2600","authenticated-orcid":true,"given":"Irina","family":"Petrache","sequence":"first","affiliation":[{"name":"Department of Medicine, Division of Pulmonary and Critical Care, National Jewish Health, Denver, Colorado, USA."},{"name":"Department of Medicine, Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado, Aurora, Colorado, 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