Marked elevations in lung and plasma ceramide in COVID-19 linked to microvascular injury Journal Article
| Authors: | Petrache, I.; Pujadas, E.; Ganju, A.; Serban, K. A.; Borowiec, A.; Babbs, B.; Bronova, I. A.; Egersdorf, N.; Hume, P. S.; Goel, K.; Janssen, W. J.; Berdyshev, E. V.; Cordon-Cardo, C.; Kolesnick, R. |
| Article Title: | Marked elevations in lung and plasma ceramide in COVID-19 linked to microvascular injury |
| Abstract: | 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-rich 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. |
| Keywords: | vascularization; endothelial cells; lung; blood vessel injury; ceramide; ceramides; respiratory distress syndrome; vascular system injuries; humans; human; coronavirus disease 2019; covid-19 |
| Journal Title: | JCI Insight |
| Volume: | 8 |
| Issue: | 10 |
| ISSN: | 2379-3708 |
| Publisher: | Amer Soc Clinical Investigation Inc |
| Date Published: | 2023-05-22 |
| Start Page: | e156104 |
| Language: | English |
| DOI: | 10.1172/jci.insight.156104 |
| PUBMED: | 37212278 |
| PROVIDER: | scopus |
| PMCID: | PMC10322682 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 June 2023 -- Source: Scopus |
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