RGD Reference Report - ACE2 activation promotes antithrombotic activity. - Rat Genome Database

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ACE2 activation promotes antithrombotic activity.

Authors: Fraga-Silva, RA  Sorg, BS  Wankhede, M  Dedeugd, C  Jun, JY  Baker, MB  Li, Y  Castellano, RK  Katovich, MJ  Raizada, MK  Ferreira, AJ 
Citation: Fraga-Silva RA, etal., Mol Med. 2010 May-Jun;16(5-6):210-5. doi: 10.2119/molmed.2009.00160. Epub 2010 Jan 22.
RGD ID: 9685451
Pubmed: PMID:20111697   (View Abstract at PubMed)
PMCID: PMC2811560   (View Article at PubMed Central)
DOI: DOI:10.2119/molmed.2009.00160   (Journal Full-text)

The aim of the present study was to test the hypothesis that the activation of the angiotensin-converting enzyme (ACE)2/angiotensin-(1-7)/Mas receptor axis by use of a novel ACE2 activator (XNT) would protect against thrombosis. Thrombi were induced in the vena cava of spontaneously hypertensive rats (SHR) and Wistar Kyoto (WKY) rats, and ACE2 and ACE activity in the thrombus was determined. Real-time thrombus formation was viewed through intravital microscopy of vessels in nude mice. Thrombus weight was 40% greater in the SHR (4.99 +/- 0.39 versus 7.04 +/- 0.66 mg). This weight increase was associated with a 20% decrease in ACE2 activity in the thrombus. In contrast, there were no differences between the WKY and SHR in ACE2 protein and ACE activity in the thrombi. ACE2 inhibition (DX600; 0.1 micromol/L/kg) increased thrombus weight by 30% and XNT treatment (10 mg/kg) resulted in a 30% attenuation of thrombus formation in the SHR. Moreover, XNT reduced platelet attachment to injured vessels, reduced thrombus size, and prolonged the time for complete vessel occlusion in mice. Thus, a decrease in thrombus ACE2 activity is associated with increased thrombus formation in SHR. Furthermore, ACE2 activation attenuates thrombus formation and reduces platelet attachment to vessels. These results suggest that ACE2 could be a novel target for the treatment of thrombogenic diseases.




  
Object Symbol
Species
Term
Qualifier
Evidence
With
Notes
Source
Original Reference(s)
ACE2Humanthrombosis treatmentISOAce2 (Rattus norvegicus) RGD 
Ace2Ratthrombosis treatmentIDA  RGD 
Ace2Mousethrombosis treatmentISOAce2 (Rattus norvegicus) RGD 


Genes (Rattus norvegicus)
Ace2  (angiotensin converting enzyme 2)

Genes (Mus musculus)
Ace2  (angiotensin converting enzyme 2)

Genes (Homo sapiens)
ACE2  (angiotensin converting enzyme 2)