Cyclooxygenase-2 inhibition improves hypercholesterolemia-induced cardiac dysfunction

Cyclooxygenase-2 inhibition improves hypercholesterolemia-induced cardiac dysfunction

Hidden cardiotoxicity is defined as cardiotoxicity of a drug that manifests only in the diseased heart. We have previously shown that the proarrhythmic hidden cardiotoxic properties of a model drug, the selective cyclooxygenase-2 inhibitor rofecoxib, can be revealed in preclinical models of ischemia...

Teljes leírás

Elmentve itt :
Bibliográfiai részletek
Szerzők: Kiss Bernadett
Nagy Regina N.
Brenner Gábor B.
Váradi Barnabás
Bihary Dóra
Ágg Bence
Makkos András
Kovácsházi Csenger
Sayour Nabil V.
Gergely Tamás G.
Husti Zoltán
Baczkó István
Reé Dóra
Apáti Ágota
Ruppert Mihály
Radovits Tamás
Merkely Béla
Poggi Paola
Chatgilialoglu Alexandros
Varga Zoltán V.
Giricz Zoltán
Ferdinandy Péter
Görbe Anikó
Dokumentumtípus: Cikk
Megjelent: 2025
Sorozat:BIOMEDICINE & PHARMACOTHERAPY 193
Tárgyszavak:
Általános orvostudomány
doi:10.1016/j.biopha.2025.118836

mtmt:36464810
Online Access:http://publicatio.bibl.u-szeged.hu/38437
Leíró adatok
Tartalmi kivonat:Hidden cardiotoxicity is defined as cardiotoxicity of a drug that manifests only in the diseased heart. We have previously shown that the proarrhythmic hidden cardiotoxic properties of a model drug, the selective cyclooxygenase-2 inhibitor rofecoxib, can be revealed in preclinical models of ischemia/reperfusion injury. As metabolic comorbidities, such as hypercholesterolemia (HC), may exacerbate hidden cardiotoxicity, we aimed to investigate the hidden cardiotoxic effects of the model drug, rofecoxib, in the presence of hypercholesterolemia. Rats were fed a high-cholesterol diet for 12 weeks and treated with 5.12 mg/kg rofecoxib. Four weeks of rofecoxib treatment surprisingly improved HC-induced mild cardiac dysfunction by restoring end-diastolic pressure, stroke work, and mechanical efficiency. Then, RNA sequencing revealed that the expression of 28 miRNAs and 300 genes was significantly altered in the HC-fed group. The HC-induced expression changes of miR-27a-5p and miR-30d-5p were reversed by rofecoxib treatment. Cdc42ep4, Cox5, and Cxcl9 genes were also counter-regulated following rofecoxib treatment compared to HC-induced changes. This is the first demonstration that rofecoxib improves HC-induced cardiac dysfunction, with the mechanism involving changes in the gene expression profile, including some key regulators of rofecoxib action.
ISSN:0753-3322

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