AI Article Synopsis
- Researchers investigated the combined effects of atorvastatin and rivaroxaban on acute pulmonary embolism (APE) in both patients and rat models, as no prior studies existed on this interaction specifically for APE.
- The combination treatment significantly reduced mean pulmonary arterial pressure (mPAP) and improved arterial oxygen levels (PaO) while decreasing oxidative stress, inflammation, and platelet activation in both patients and rats.
- The study concluded that the therapeutic effects of rivaroxaban and atorvastatin are linked to the increased expression of specific proteins, NRF2 and NQO1, which play crucial roles in managing APE.
Article Abstract
Background: Atorvastatin and direct oral factor Xa inhibitors (for instance, rivaroxaban) are co-administrated in patients with atrial fibrillation. However, no studies have been conducted on the function of these two agents in acute pulmonary embolism (APE). Therefore, we investigated the effects of rivaroxaban + atorvastatin in rats with APE and explored the underlying mechanisms.
Methods: Patients with APE were enrolled, and rats with APE were generated for different regimens. The mean pulmonary arterial pressure (mPAP), heart rate, and PaO of APE patients and rats were measured. The plasma levels of oxidative stress- and inflammation-related factors were measured, and the expression of platelet activation markers (CD63 and CD62P) was detected. The proteins targeted by rivaroxaban and atorvastatin, the targets associated with APE, and the genes aberrantly expressed in rats with APE were intersected to obtain candidate factors.
Results: Rivaroxaban + atorvastatin reduced mPAP and increased PaO in patients and rats with APE. Rivaroxaban + atorvastatin repressed oxidative stress, inflammatory levels, and platelet activation during APE. NRF2 and NQO1 were increased in the lung of rats treated with rivaroxaban + atorvastatin. The therapeutic effect of the combination on APE rats was suppressed after NRF2 downregulation. NRF2 promoted the NQO1 transcription. NQO1 eliminated the inhibitory effect of sh-NRF2 on the combined therapy.
Conclusion: The alleviating effect of rivaroxaban + atorvastatin administration against APE correlates with NRF2/NQO1 expression.
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| http://dx.doi.org/10.1007/s10557-023-07479-4 | DOI Listing |
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