A novel peptide from yak ameliorates hypoxia-induced cardiac dysfunction via targeting gut microbiota and HIF-1α pathway

ABSTRACT: Due to the high altitude and low oxygen levels, individuals residing or traveling in high-altitude regions often experience hypoxic cardiac dysfunction, which significantly affects their overall well-being and quality of life. Our previous investigations showed that peptide from yak milk residue exhibits notable antioxidant, anti-inflammatory, and anti-apoptotic properties that may have a good regulatory effect on hypoxic cardiac dysfunction. In this study, our results suggest that oral administration of yak milk peptide T3 improves the cardiac dysfunction of mice by the hypoxia-inducible factor 1α (HIF-1α) pathway, and these results may be related to the regulation of T3 on the gut microbiota of mice. Additionally, oral administration T3 enhances the permeability of the intestinal barrier and reduces intestinal inflammation. Further analysis revealed that the genera Oscillospira, Clostridium, and Staphylococcus are associated with aspartate aminotransferase, lactate dehydrogenase, and reactive oxygen species levels in heart tissues, which could ameliorate hypoxia-induced myocardial injury in mice. In vitro cell models have also confirmed that T3 intervention can activate the HIF-1α pathway and inhibit myocardial inflammation and cardiomyocyte apoptosis. These findings suggest that T3 may be a potential candidate for developing functional foods to reduce hypoxia-induced cardiac dysfunction.