tetano
Editor, Senior Moderator
Nat Cardiovasc Res
. 2023 Oct;2(10):899-916.
doi: 10.1038/s44161-023-00336-5. Epub 2023 Sep 28. SARS-CoV-2 infection triggers pro-atherogenic inflammatory responses in human coronary vessels
Natalia Eberhardt[SUP] 1 [/SUP], Maria Gabriela Noval[SUP] 2 [/SUP], Ravneet Kaur[SUP] 1 [/SUP], Letizia Amadori[SUP] 1 [/SUP], Michael Gildea[SUP] 1 [/SUP], Swathy Sajja[SUP] 1 [/SUP], Dayasagar Das[SUP] 1 [/SUP], Burak Cilhoroz[SUP] 1 [/SUP], O'Jay Stewart[SUP] 3 [/SUP], Dawn M Fernandez[SUP] 4 [/SUP], Roza Shamailova[SUP] 1 [/SUP], Andrea Vasquez Guillen[SUP] 1 [/SUP], Sonia Jangra[SUP] 5 [/SUP], Michael Schotsaert[SUP] 5 [/SUP], Jonathan D Newman[SUP] 1 [/SUP], Peter Faries[SUP] 6 [/SUP], Thomas Maldonado[SUP] 7 [/SUP], Caron Rockman[SUP] 7 [/SUP], Amy Rapkiewicz[SUP] 8 [/SUP], Kenneth A Stapleford[SUP] 2 [/SUP], Navneet Narula[SUP] 9 [/SUP], Kathryn J Moore[SUP] 1 [/SUP], Chiara Giannarelli[SUP] 1 3 9 [/SUP]
Affiliations
Patients with coronavirus disease 2019 (COVID-19) present increased risk for ischemic cardiovascular complications up to 1 year after infection. Although the systemic inflammatory response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection likely contributes to this increased cardiovascular risk, whether SARS-CoV-2 directly infects the coronary vasculature and attendant atherosclerotic plaques remains unknown. Here we report that SARS-CoV-2 viral RNA is detectable and replicates in coronary lesions taken at autopsy from severe COVID-19 cases. SARS-CoV-2 targeted plaque macrophages and exhibited a stronger tropism for arterial lesions than adjacent perivascular fat, correlating with macrophage infiltration levels. SARS-CoV-2 entry was increased in cholesterol-loaded primary macrophages and dependent, in part, on neuropilin-1. SARS-CoV-2 induced a robust inflammatory response in cultured macrophages and human atherosclerotic vascular explants with secretion of cytokines known to trigger cardiovascular events. Our data establish that SARS-CoV-2 infects coronary vessels, inducing plaque inflammation that could trigger acute cardiovascular complications and increase the long-term cardiovascular risk.
. 2023 Oct;2(10):899-916.
doi: 10.1038/s44161-023-00336-5. Epub 2023 Sep 28. SARS-CoV-2 infection triggers pro-atherogenic inflammatory responses in human coronary vessels
Natalia Eberhardt[SUP] 1 [/SUP], Maria Gabriela Noval[SUP] 2 [/SUP], Ravneet Kaur[SUP] 1 [/SUP], Letizia Amadori[SUP] 1 [/SUP], Michael Gildea[SUP] 1 [/SUP], Swathy Sajja[SUP] 1 [/SUP], Dayasagar Das[SUP] 1 [/SUP], Burak Cilhoroz[SUP] 1 [/SUP], O'Jay Stewart[SUP] 3 [/SUP], Dawn M Fernandez[SUP] 4 [/SUP], Roza Shamailova[SUP] 1 [/SUP], Andrea Vasquez Guillen[SUP] 1 [/SUP], Sonia Jangra[SUP] 5 [/SUP], Michael Schotsaert[SUP] 5 [/SUP], Jonathan D Newman[SUP] 1 [/SUP], Peter Faries[SUP] 6 [/SUP], Thomas Maldonado[SUP] 7 [/SUP], Caron Rockman[SUP] 7 [/SUP], Amy Rapkiewicz[SUP] 8 [/SUP], Kenneth A Stapleford[SUP] 2 [/SUP], Navneet Narula[SUP] 9 [/SUP], Kathryn J Moore[SUP] 1 [/SUP], Chiara Giannarelli[SUP] 1 3 9 [/SUP]
Affiliations
- PMID: 38076343
- PMCID: PMC10702930
- DOI: 10.1038/s44161-023-00336-5
Patients with coronavirus disease 2019 (COVID-19) present increased risk for ischemic cardiovascular complications up to 1 year after infection. Although the systemic inflammatory response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection likely contributes to this increased cardiovascular risk, whether SARS-CoV-2 directly infects the coronary vasculature and attendant atherosclerotic plaques remains unknown. Here we report that SARS-CoV-2 viral RNA is detectable and replicates in coronary lesions taken at autopsy from severe COVID-19 cases. SARS-CoV-2 targeted plaque macrophages and exhibited a stronger tropism for arterial lesions than adjacent perivascular fat, correlating with macrophage infiltration levels. SARS-CoV-2 entry was increased in cholesterol-loaded primary macrophages and dependent, in part, on neuropilin-1. SARS-CoV-2 induced a robust inflammatory response in cultured macrophages and human atherosclerotic vascular explants with secretion of cytokines known to trigger cardiovascular events. Our data establish that SARS-CoV-2 infects coronary vessels, inducing plaque inflammation that could trigger acute cardiovascular complications and increase the long-term cardiovascular risk.