Apixaban attenuates ischemia-induced myocardial fibrosis by inhibition of Gq/PKC signaling.

Apixaban attenuates ischemia-induced myocardial fibrosis by inhibition of Gq/PKC signaling. Biochem Biophys Res Commun. 2018 Apr 11;: Authors: Shi G, Yang X, Pan M, Sun J, Ke H, Zhang C, Geng H Abstract It was previously found that patients with symptom of myocardial dysfunction had increased levels of thrombin. Apixaban is one of the novel oral anticoagulant drugs widely used in clinic. As the inhibitor of FXa (prothrombin), it inhibits prothrombin conversion into thrombin leading to thrombin deficiency in vivo. However, the effects of apixaban on myocardial fibrosis were still unclear, and the concomitant molecular mechanisms remain to be investigated. Here, we showed that myocardial fibrosis-bearing mice induced by continuous myocardial ischemia (MI) had higher levels of thrombin. Orally administration of apixaban significantly abrogated fibrosis condition and thrombin levels. In vitro, thrombin induced collagen deposition in primary cardiac fibroblasts in a dose-dependent manner. Mechanistic experiments showed that thrombin induced collagen deposition by activation of the Par-1-coupled Gq/PKC signaling. Genetic ablation of Gq or pharmacological inhibition of PKC effectively blunted thrombin-induced collagen deposition in cardiac fibroblasts. Moreover, administration of PKC inhibitor or Gq antagonist obviously blocked MI-induced myocardial fibrosis in mice. To conclude, apixaban attenuates MI-induced myocardial fibrosis by inhibit...
Source: Biochemical and Biophysical Research communications - Category: Biochemistry Authors: Tags: Biochem Biophys Res Commun Source Type: research