Ace2 Activation Promotes Antithrombotic Activity

Abstract

Hyperactivity of the axis ACE/AngII/AT1R of the renin‐angiotensin system is associated with occurrence of acute thrombotic event. Recently a novel concept of a counterrugulatory axis, ACE2/Ang‐(1‐7)/Mas, has emerged. We hypothesized that ACE2 would be protective against thrombosis. Thrombus was induced in the vena cava of SHR and WKY rats by FeCl3 solution. ACE2 and ACE protein expression and activities in the thrombus were determined by Western blot and fluorogenic kinetic assays, respectively. Real time thrombus formation was visualized by intravital microscopy of the vessels of nude mice. Ferric chloride‐induced thrombus weight was 40% higher in the SHR compared to WKY rats. This was associated with a 20% decreased in ACE2 activity in the thrombus of the SHR. In contrast, ACE2 protein expression and ACE activity did not differ between the thrombus of WKY rats and SHR. Inhibition of ACE2 by DX600 increased the thrombus weight by 30%, preferentially in the SHR. Furthermore, treatment with XNT resulted in a 30% attenuation of thrombus formation in both the SHR and WKY. In addition, XNT treatment prolonged the time for complete vessel occlusion and reduced thrombus size when observed under real‐time intravital microscopy. Our data demonstrated that a decrease in ACE2 activity is associated with increased thrombus formation in the SHR. Furthermore, activation of ACE2 attenuates thrombus formation.

Severe Acute Respiratory Syndrome Coronavirus 2, COVID-19, and the Renin-Angiotensin System

“…74 A small study of patients with moderate-to-severe COVID-19, in fact, showed improvement in oxygen saturation and reduced alveolar effusion after treatment with plasminogen. 30 Moreover, ACE2 is, in general, an antithrombotic enzyme, 75 such that loss of ACE2 via internalization with the virus or enhanced shedding 76 could exacerbate the coagulopathy. Loss of ACE2 promotes higher levels of Ang II, and Ang II potently upregulates PAI-1 expression, among other pro-coagulant actions.…”

Zinc (Ⅱ)-Induced Anti-Thrombus Formation against Severe COVID-19 Infection

“…Zinc induced ACE2 activation promotes activity of anti-thrombus formation and growth against COVID-19 infection. Zinc activates COVID-19 ACE2 as entry receptor that zinc induced ACE2 activation promotes the activity of anti-thrombus formation growth, in which ACE2 activation decreases thrombus formation and reduces platelet attachment to vessels [30]. Further, treatment of zinc supplement for cardiovascular diseases (CVD) and COVID-19 comorbidity should be treat preventing viral replication by inhibiting the RNA-Dependent RNA Polymerase (RdRp) of the SARS-CoV-2, and enhance protective immune responses, and restoring functional balance of ACE2 [31].…”