Metoprolol (Met) is widely applied in the treatment ofmyocardial infarctionand coronary heart disease in clinic. However, the metabolic network in vivo affected by Met manipulation is still unclear and its therapeutic molecular mechanisms were remained to be furthered elucidated except 1 adrenergic receptor.Myocardial infarction(MI) was induced by permanent CAL for 24 h in ICR mice.Myocardialinfarct size, biochemical indicators such as creatine kinase (CK), lactate dehydrogenase (LDH), C-reactive Protein (CRP), tumor necrosis factor- (TNF-) and cardiac troponin I(cTn-I), cardiac function andmyocardialpathological changes were detected to ensure the improvement of Met on MI. Subsequently, the significantly changed endogenous metabolites and the network in both serum and urine were screened and constructed through metabolomics by using HPLC-Q-TOF/MS. Finally, the potential regulatory enzymes that could be the possible new therapeutic targets of Met were selected and validated by western blotting and immunohistochemistry based on the screened differential metabolites and the enrichment analysis.

Met effectively reduced the infarct size ofmyocardial infarctionmice, improved the biochemical indicators, and ameliorated the cardiac function and pathological conditions. Our study further found that Met could regulate the pathways of glycine, serine and threonine metabolism, cysteine and methionine metabolism, purine and pyrimidine metabolism under the pathological conditions of MI. Moreover, several regulatory enzymes involved GATM, CSE and NT5E were demonstrated to be regulated by Met. This study constructed the regulatory metabolic network map of Met, elucidated the endogenous metabolic pathway regulated by Met, and validated the new potential therapeutic targets of Met in MI, which might provide a further reference for the clinical application of Met.

Go here to read the rest:
Metabolomic Profiling of Metoprolol-Induced Cardioprotection in a Murine Model of Acute Myocardial Ischemia - DocWire News