SARS-CoV-2 Spike Protein Impairs Endothelial Function via Downregulation of ACE2.
Yuyang LeiJiao ZhangCara R SchiavonMing HeLili ChenHui ShenYichi ZhangQian YinYoshitake ChoLeonardo AndradeGerry S ShadelMark HepokoskiTing LeiHongliang WangJin ZhangJason X-J YuanAtul MalhotraUri ManorShengpeng WangZu-Yi YuanJohn Y-J ShyyPublished in: bioRxiv : the preprint server for biology (2020)
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.
Keyphrases
- angiotensin converting enzyme
- angiotensin ii
- coronavirus disease
- sars cov
- endothelial cells
- binding protein
- cell proliferation
- respiratory syndrome coronavirus
- protein protein
- oxidative stress
- signaling pathway
- poor prognosis
- amino acid
- induced apoptosis
- skeletal muscle
- small molecule
- long non coding rna
- risk factors
- transcription factor
- nitric oxide synthase
- endoplasmic reticulum stress
- high glucose