tetano
Editor, Senior Moderator
Nat Cardiovasc Res
. 2024 Oct;3(10):1249-1265.
doi: 10.1038/s44161-024-00543-8. Epub 2024 Oct 14. CCL2-mediated endothelial injury drives cardiac dysfunction in long COVID
Dilip Thomas[SUP] #[/SUP][SUP] 1 2 [/SUP], Chikage Noishiki[SUP] #[/SUP][SUP] 1 3 [/SUP], Sadhana Gaddam[SUP] #[/SUP][SUP] 4 [/SUP], David Wu[SUP] 1 3 [/SUP], Amit Manhas[SUP] 1 2 [/SUP], Yu Liu[SUP] 1 2 [/SUP], Dipti Tripathi[SUP] 1 3 5 [/SUP], Nimish Kathale[SUP] 6 [/SUP], Shaunak S Adkar[SUP] 3 5 [/SUP], Jaishree Garhyan[SUP] 7 [/SUP], Chun Liu[SUP] 8 [/SUP], Baohui Xu[SUP] 3 [/SUP], Elsie G Ross[SUP] 9 [/SUP], Ronald L Dalman[SUP] 1 3 [/SUP], Kevin C Wang[SUP] 4 [/SUP], Anthony E Oro[SUP] 4 [/SUP], Karim Sallam[SUP] 1 2 [/SUP], Jason T Lee[SUP] 3 5 [/SUP], Joseph C Wu[SUP] 1 2 10 [/SUP], Nazish Sayed[SUP] 11 12 13 14 [/SUP]
Affiliations
Evidence linking the endothelium to cardiac injury in long coronavirus disease (COVID) is well documented, but the underlying mechanisms remain unknown. Here we show that cytokines released by endothelial cells (ECs) contribute to long-COVID-associated cardiac dysfunction. Using thrombotic vascular tissues from patients with long COVID and induced pluripotent stem cell-derived ECs (iPSC-ECs), we modeled endotheliitis and observed similar dysfunction and cytokine upregulation, notably CCL2. Cardiac organoids comprising iPSC-ECs and iPSC-derived cardiomyocytes showed cardiac dysfunction after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exposure, driven by CCL2. Profiling of chromatin accessibility and gene expression at a single-cell resolution linked CCL2 to 'phenotype switching' and cardiac dysfunction, validated by high-throughput proteomics. Disease modeling of cardiac organoids and exposure of human ACE2 transgenic mice to SARS-CoV-2 spike proteins revealed that CCL2-induced oxidative stress promoted post-translational modification of cardiac proteins, leading to cardiac dysfunction. These findings suggest that EC-released cytokines contribute to cardiac dysfunction in long COVID, highlighting the importance of early vascular health monitoring in patients with long COVID.
. 2024 Oct;3(10):1249-1265.
doi: 10.1038/s44161-024-00543-8. Epub 2024 Oct 14. CCL2-mediated endothelial injury drives cardiac dysfunction in long COVID
Dilip Thomas[SUP] #[/SUP][SUP] 1 2 [/SUP], Chikage Noishiki[SUP] #[/SUP][SUP] 1 3 [/SUP], Sadhana Gaddam[SUP] #[/SUP][SUP] 4 [/SUP], David Wu[SUP] 1 3 [/SUP], Amit Manhas[SUP] 1 2 [/SUP], Yu Liu[SUP] 1 2 [/SUP], Dipti Tripathi[SUP] 1 3 5 [/SUP], Nimish Kathale[SUP] 6 [/SUP], Shaunak S Adkar[SUP] 3 5 [/SUP], Jaishree Garhyan[SUP] 7 [/SUP], Chun Liu[SUP] 8 [/SUP], Baohui Xu[SUP] 3 [/SUP], Elsie G Ross[SUP] 9 [/SUP], Ronald L Dalman[SUP] 1 3 [/SUP], Kevin C Wang[SUP] 4 [/SUP], Anthony E Oro[SUP] 4 [/SUP], Karim Sallam[SUP] 1 2 [/SUP], Jason T Lee[SUP] 3 5 [/SUP], Joseph C Wu[SUP] 1 2 10 [/SUP], Nazish Sayed[SUP] 11 12 13 14 [/SUP]
Affiliations
- PMID: 39402206
- DOI: 10.1038/s44161-024-00543-8
Evidence linking the endothelium to cardiac injury in long coronavirus disease (COVID) is well documented, but the underlying mechanisms remain unknown. Here we show that cytokines released by endothelial cells (ECs) contribute to long-COVID-associated cardiac dysfunction. Using thrombotic vascular tissues from patients with long COVID and induced pluripotent stem cell-derived ECs (iPSC-ECs), we modeled endotheliitis and observed similar dysfunction and cytokine upregulation, notably CCL2. Cardiac organoids comprising iPSC-ECs and iPSC-derived cardiomyocytes showed cardiac dysfunction after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exposure, driven by CCL2. Profiling of chromatin accessibility and gene expression at a single-cell resolution linked CCL2 to 'phenotype switching' and cardiac dysfunction, validated by high-throughput proteomics. Disease modeling of cardiac organoids and exposure of human ACE2 transgenic mice to SARS-CoV-2 spike proteins revealed that CCL2-induced oxidative stress promoted post-translational modification of cardiac proteins, leading to cardiac dysfunction. These findings suggest that EC-released cytokines contribute to cardiac dysfunction in long COVID, highlighting the importance of early vascular health monitoring in patients with long COVID.
