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. 2010 May-Jun;16(5-6):210-5.
doi: 10.2119/molmed.2009.00160. Epub 2010 Jan 22.

ACE2 activation promotes antithrombotic activity

Affiliations

ACE2 activation promotes antithrombotic activity

Rodrigo A Fraga-Silva et al. Mol Med. 2010 May-Jun.

Abstract

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.

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Figures

Figure 1
Figure 1
Increased thrombus formation in SHR is associated with lower ACE2 activity in thrombi. (A) FeCl2-induced thrombus weight in SHR and WKY; (B) ACE2 activity in thrombi from SHR and WKY; (C) Representative Western blotting analysis of ACE2 levels. Data were normalized by using β-actin. (D) Quantification of Western blotting data. *P < 0.05 versus WKY (unpaired Student t test, n = 8 to 10). A.U., arbitrary units.
Figure 2
Figure 2
ACE and ACE2 activity in thrombi of SHR and WKY rats. (A) ACE activity in thrombi of SHR and WKY. No significant differences were found between SHR and WKY. (B) Ratio between ACE2/ACE activity in thrombi of SHR and WKY. *P < 0.05 versus WKY (unpaired Student t test, n = 10 to 11). A.U., arbitrary units.
Figure 3
Figure 3
Antithrombotic effect of XNT on rats. FeCl2-induced thrombus weight in WKY and SHR treated with (A) DX600 and (B) XNT. *P < 0.05 (unpaired Student t test). (C) ACE2 activity in thrombi of WKY and SHR treated with either XNT or DX600. *P < 0.05 versus WKY rats, #P < 0.05 versus untreated SHR (one-way ANOVA followed by the Bonferroni posttest). Each column represents mean ± SEM (n = 7 to 9).
Figure 4
Figure 4
Effect of XNT on thrombus development and time for thrombus formation. (A) Representative photomicrographs showing thrombi development in dorsal skin vessels in nude mice recorded by use of intravital microscopy. The upper panel shows thrombi development in a control animal 1, 8 and 12 min after FeCl3 application. The lower panel shows thrombi development in an XNT-treated mouse 1, 8 and 12 min after FeCl3 application. Arrows indicate thrombi. (B) Ratio between thrombi area/vessel area. *P < 0.05 versus XNT treatment (two-way ANOVA followed by the Bonferroni posttest; n = 6 to 7). (C) Time for thrombus formation after FeCl3 application. Each column represents mean ±SEM (n = 6 to 7). *P < 0.05 versus vehicle (unpaired Student t test).

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References

    1. Willoughby S, Holmes A, Loscalzo J. Platelets and cardiovascular disease. Eur J Cardiovasc Nurs. 2002;1:273–88. - PubMed
    1. Lip GY. Hypertension, platelets, and the endothelium: the “thrombotic paradox” of hypertension (or “Birmingham paradox”) revisited. Hypertension. 2003;41:199–200. - PubMed
    1. Dzau VJ. Theodore Cooper Lecture: Tissue angiotensin and pathobiology of vascular disease: a unifying hypothesis. Hypertension. 2001;37:1047–52. - PubMed
    1. Donoghue M, et al. A novel angiotensin-converting enzyme-related carboxypeptidase (ACE2) converts angiotensin I to angiotensin 1–9. Circ. Res. 2000;87:E1–9. - PubMed
    1. Ferreira AJ, Raizada MK. Genomic and proteomic approaches for targeting of angiotensin-converting enzyme 2 for cardiovascular diseases. Curr Opin Cardiol. 2008;23:364–9. - PubMed

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