Yang Chen, Cuncun Fan, Jinkun Wang, Mingming Jiang
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引用次数: 0
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 PaO2 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 PaO2 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.
期刊介绍：
Designed to objectively cover the process of bench to bedside development of cardiovascular drug, device and cell therapy, and to bring you the information you need most in a timely and useful format, Cardiovascular Drugs and Therapy takes a fresh and energetic look at advances in this dynamic field.
Homing in on the most exciting work being done on new therapeutic agents, Cardiovascular Drugs and Therapy focusses on developments in atherosclerosis, hyperlipidemia, diabetes, ischemic syndromes and arrhythmias. The Journal is an authoritative source of current and relevant information that is indispensable for basic and clinical investigators aiming for novel, breakthrough research as well as for cardiologists seeking to best serve their patients.
Providing you with a single, concise reference tool acknowledged to be among the finest in the world, Cardiovascular Drugs and Therapy is listed in Web of Science and PubMed/Medline among other abstracting and indexing services. The regular articles and frequent special topical issues equip you with an up-to-date source defined by the need for accurate information on an ever-evolving field. Cardiovascular Drugs and Therapy is a careful and accurate guide through the maze of new products and therapies which furnishes you with the details on cardiovascular pharmacology that you will refer to time and time again.
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