SARS-CoV-2 Spike Protein Impairs Endothelial Function via Downregulation of ACE2
Coronavirus disease 2019 (COVID-19) includes the cardiovascular complications in addition to respiratory disease. SARS-CoV-2 infection impairs endothelial function and induces vascular inflammation, leading to endotheliitis. SARS-CoV-2 infection relies on the binding of Spike glycoprotein (S protein) to angiotensin converting enzyme 2 (ACE2) in the host cells. We show here that S protein alone can damage vascular endothelial cells (ECs) in vitro and in vivo, manifested by impaired mitochondrial function, decreased ACE2 expression and eNOS activity, and increased glycolysis. The underlying mechanism involves S protein downregulation of AMPK and upregulation of MDM2, causing ACE2 destabilization. Thus, the S protein-exerted vascular endothelial damage via ACE2 downregulation overrides the decreased virus infectivity.
| Errataetall: | |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2020 |
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| Enthalten in: |
bioRxiv : the preprint server for biology - (2020) vom: 04. Dez. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Lei, Yuyang [VerfasserIn] |
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| Anmerkungen: |
Date Revised 29.04.2021 published: Electronic UpdateIn: Circ Res. 2021 Mar 31;:. - PMID 33784827 Citation Status PubMed-not-MEDLINE |
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| doi: |
10.1101/2020.12.04.409144 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM318654105 |
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| 500 | |a published: Electronic | ||
| 500 | |a UpdateIn: Circ Res. 2021 Mar 31;:. - PMID 33784827 | ||
| 500 | |a Citation Status PubMed-not-MEDLINE | ||
| 520 | |a Coronavirus disease 2019 (COVID-19) includes the cardiovascular complications in addition to respiratory disease. SARS-CoV-2 infection impairs endothelial function and induces vascular inflammation, leading to endotheliitis. SARS-CoV-2 infection relies on the binding of Spike glycoprotein (S protein) to angiotensin converting enzyme 2 (ACE2) in the host cells. We show here that S protein alone can damage vascular endothelial cells (ECs) in vitro and in vivo, manifested by impaired mitochondrial function, decreased ACE2 expression and eNOS activity, and increased glycolysis. The underlying mechanism involves S protein downregulation of AMPK and upregulation of MDM2, causing ACE2 destabilization. Thus, the S protein-exerted vascular endothelial damage via ACE2 downregulation overrides the decreased virus infectivity | ||
| 650 | 4 | |a Preprint | |
| 700 | 1 | |a Zhang, Jiao |e verfasserin |4 aut | |
| 700 | 1 | |a Schiavon, Cara R |e verfasserin |4 aut | |
| 700 | 1 | |a He, Ming |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Lili |e verfasserin |4 aut | |
| 700 | 1 | |a Shen, Hui |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Yichi |e verfasserin |4 aut | |
| 700 | 1 | |a Yin, Qian |e verfasserin |4 aut | |
| 700 | 1 | |a Cho, Yoshitake |e verfasserin |4 aut | |
| 700 | 1 | |a Andrade, Leonardo |e verfasserin |4 aut | |
| 700 | 1 | |a Shadel, Gerry S |e verfasserin |4 aut | |
| 700 | 1 | |a Hepokoski, Mark |e verfasserin |4 aut | |
| 700 | 1 | |a Lei, Ting |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Hongliang |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Jin |e verfasserin |4 aut | |
| 700 | 1 | |a Yuan, Jason X-J |e verfasserin |4 aut | |
| 700 | 1 | |a Malhotra, Atul |e verfasserin |4 aut | |
| 700 | 1 | |a Manor, Uri |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Shengpeng |e verfasserin |4 aut | |
| 700 | 1 | |a Yuan, Zu-Yi |e verfasserin |4 aut | |
| 700 | 1 | |a Shyy, John Y-J |e verfasserin |4 aut | |
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