A Novel Mechanism of 16α-OHE1, One of Estrogen Metabolites, Alleviating Inflammatory Infiltration in Hypoxia-Induced Myocardial Injury via β2-Adrenergic Receptor

Abstract

Objective The study aimed to investigate the protective effect of 16α-OHE1 on myocardial injury caused by hypoxia.Methods and results Rats were exposed to normoxia or hypoxia conditions simulating an high altitude of 6000 m in a low-pressure chamber for 7 days. Post-exposure, evaluations were made on cardiac function, myocardial enzyme concentrations, histopathological modifications, inflammatory infiltration, and β2-adrenergic receptor (β2AR) expression levels. In parallel, H9C2 cells were cultured under standard oxygen conditions or in a three-gas incubator containing 5% O2 for 24 h. Cell viability, apoptosis, inflammatory infiltration, and myocardial enzyme levels in H9C2 cells were measured. Hypoxia induced significant myocardial damage, marked by impaired cardiac function, myocardial structural changes, inflammatory infiltration, and increased apoptosis. Pre-treatment with 16α-OHE1 significantly improved heart function and reduced myocardial enzyme release. The increased inflammatory response was also significantly suppressed. In addition to preserving myocardial structures, hypoxia-induced apoptosis in cardiomyocytes was significantly weakened. Notably, these protective effects of 16α-OHE1 were linked with the upregulation of β2AR expression. However, when β2AR was inhibited by ICI 118,551, the protective effect of 16α-OHE1 on the myocardium was abrogated.Conclusion 16α-OHE1 could reduce hypoxia-induced myocardial injury in rats through β2-adrenoceptors.