General Information:

Id: 11,830 (click here to show other Interactions for entry)
Diseases: SARS-CoV infection
Mus musculus
article
Reference: Kuba K et al.(2005) A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus-induced lung injury Nat. Med. 11: 875-879 [PMID: 16007097]

Interaction Information:

Comment ACE2 functions as a carboxypeptidase, cleaving a single residue from angiotensin I (AngI), generating Ang1-9, and a single residue from angiotensin II (AngII) to generate Ang1-7. The ACE2 homologue ACE, by contrast, cleaves the decapeptide AngI into the octapeptide AngII. Thus, ACE2 counterbalances the function of ACE and negatively regulates AngII production. To test whether Spike-Fc injections indeed affect the function of the renin-angiotensin system, AngII levels in the lungs of acid- and Spike-Fc–treated mice were analyzed. Acid aspiration increased AngII levels in the lungs of wild-type mice. Notably, the authors observed a further, significant increase in AngII levels in the lung tissue of mice treated with Spike-Fc.
Formal Description
Interaction-ID: 116886

environment

SARS-CoV S protein

increases_quantity of

gene/protein

Angiotensin II

in the lung
Comment To confirm whether Spike-Fc promotes lung disease pathogenesis through increased AngII production and functional alterations of the renin-angiotensin system, the authors blocked the AngII receptor type 1 (AT1R) with a specific inhibitor. The AT1R is the crucial receptor that mediates AngII-induced vascular permeability and severe acute lung injury. Inhibition of the AT1R indeed attenuated acute severe lung injury in Spike-Fc–treated mice. Inhibition of the AT1R also attenuated pulmonary edema. Taken together, the data show that SARS-CoV Spike can exaggerate acute lung failure through deregulation of the renin-angiotensin system. Moreover, SARS-CoV Spike–mediated lung failure can be rescued by inhibition of AT1R.
Formal Description
Interaction-ID: 116888

gene/protein

AGTR1

affects_activity of

phenotype

pulmonary edema

in SARS-CoV S protein-treated mice
Drugbank entries Show/Hide entries for AGTR1
Comment Decreased ACE2 protein, but normal ACE levels, were found in the lungs of SARS-CoV–infected mice.
Formal Description
Interaction-ID: 119082

disease

SARS-CoV infection

decreases_quantity of

gene/protein

ACE2

in the lung
Drugbank entries Show/Hide entries for ACE2