%0 Journal Article
%T 16α-OHE1 alleviates hypoxia-induced inflammation and myocardial damage via the activation of β2-Adrenergic receptor.
%A Zhou Y
%A Yin Z
%A Cui J
%A Wang C
%A Fu T
%A Adu-Amankwaah J
%A Fu L
%A Zhou X
%J Mol Cell Endocrinol
%V 587
%N 0
%D 2024 Jun 1
%M 38518841
%F 4.369
%R 10.1016/j.mce.2024.112200
%X OBJECTIVE: Myocardial injuries resulting from hypoxia are a significant concern, and this study aimed to explore potential protective strategies against such damage. Specifically, we sought to investigate the cardioprotective effects of 16α-hydroxyestrone (16α-OHE1).
METHODS: Male Sprague‒Dawley (SD) rats were subjected to hypoxic conditions simulating high-altitude exposure at 6000 m in a low-pressure chamber for 7 days. Before and during hypoxic exposure, estradiol (E2) and various doses of 16α-OHE1 were administered for 14 days. Heart weight/body weight (HW/BW), myocardial structure, Myocardial injury indicators and inflammatory infiltration in rats were measured. H9C2 cells cultured under 5% O2 conditions received E2 and varying doses of 16α-OHE1; Cell viability, apoptosis, inflammatory infiltration, and Myocardial injury indicators were determined. Expression levels of β2AR were determined in rat hearts and H9C2 cells. The β2AR inhibitor, ICI 118,551, was employed to investigate β2AR's role in 16α-OHE1's cardioprotective effects.
RESULTS: Hypoxia led to substantial myocardial damage, evident in increased heart HW, CK-MB, cTnT, ANP, BNP, structural myocardial changes, inflammatory infiltration, and apoptosis. Pre-treatment with E2 and 16α-OHE1 significantly mitigated these adverse changes. Importantly, the protective effects of E2 and 16α-OHE1 were associated with the upregulation of β2AR expression in both rat hearts and H9C2 cells. However, inhibition of β2AR by ICI 118,551 in H9C2 cells nullified the protective effect of 16α-OHE1 on myocardium.
CONCLUSIONS: Our findings suggest that 16α-OHE1 can effectively reduce hypoxia-induced myocardial injury in rats through β2ARs, indicating a promising avenue for cardioprotection.