Cardioprotective potential of compound 3K, a selective PKM2 inhibitor in isoproterenol-induced acute myocardial infarction: A mechanistic study.
Toxicol Appl Pharmacol
; 485: 116905, 2024 Apr.
Article
en En
| MEDLINE
| ID: mdl-38521371
ABSTRACT
Myocardial infarction (MI) or heart attack arises from acute or chronic prolonged ischemic conditions in the myocardium. Although several risk factors are associated with MI pathophysiology, one of the risk factors is an imbalance in the oxygen supply. The current available MI therapies are still inadequate due to the complexity of MI pathophysiology. Pyruvate kinase M2 (PKM2) has been implicated in numerous CVDs pathologies. However, the effect of specific pharmacological intervention targeting PKM2 has not been studied in MI. Therefore, in this study, we explored the effect of compound 3K, a PKM2-specific inhibitor, in isoproterenol-induced acute MI model. In this study, in order to induce MI in rats, isoproterenol (ISO) was administered at a dose of 100 mg/kg over two days at an interval of 24 h. Specific PKM2 inhibitor, compound 3K (2 and 4 mg/kg), was administered in MI rats to investigate its cardioprotective potential. After the last administration of compound 3K, ECG and hemodynamic parameters were recorded using a PV-loop system. Cardiac histology, western blotting, and plasmatic cardiac damage markers were evaluated to elucidate the underlying mechanisms. Treatment of compound 3K significantly reduced ISO-induced alterations in ECG, ventricular functions, cardiac damage, infarct size, and cardiac fibrosis. Compound 3K treatment produced significant increase in PKM1 expression and decrease in PKM2 expression. In addition, HIF-1α, caspase-3, c-Myc, and PTBP1 expression were also reduced after compound 3K treatment. This study demonstrates the cardioprotective potential of compound 3K in MI, and its mechanisms of cardioprotective action.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Piruvato Quinasa
/
Cardiotónicos
/
Isoproterenol
/
Infarto del Miocardio
Límite:
Animals
Idioma:
En
Revista:
Toxicol Appl Pharmacol
Año:
2024
Tipo del documento:
Article
País de afiliación:
India
Pais de publicación:
Estados Unidos