Qianyang Yuyin granule modulates glycolysis and inflammatory response to treat hypertensive cardiac remodeling.

OBJECTIVE

To investigate the effect of Qianyang Yuyin granule (QYYY) on AngII-induced hypertensive cardiac remodeling, focusing on the role of pyruvate kinase isozyme M2 (PKM2) mediated glycolysis.

METHODS

A hypertensive mouse model was established in male C57BL/6 mice by continuous infusion of angiotensin II (AngII; 1000 ng·kg-1·min-1). Mice were administered varying doses of QYYY, with sacubitril/ valsartan (Sac/Val) serving as the positive control. Parameters evaluated included blood pressure, cardiac function, hypertrophy, fibrosis, inflammation, and apoptosis. The metabolic profile of myocardial tissue was analyzed using ultra performance liquid chromatography tandem mass spectrometry. Additionally, the involvement of the hypoxia-inducible factor 1-alpha (HIF-1α)/PKM2 signaling pathway was examined by Western blotting and immunohistochemistry.

RESULTS

QYYY significantly lowered blood pressure, attenuated cardiac hypertrophy and fibrosis, reduced serum levels of inflammatory factors tumor necrosis factor-α and tumor necrosis factor-β, and decreased activation of phospho-NF-kappa B p65 pathway in cardiac tissue of hypertensive mice. Metabolomic analysis indicated that QYYY ameliorated cardiometabolic dysfunction, primarily associated with energy and amino acid metabolism, involving modulation of the HIF-1α/PKM2-mediated glycolytic pathway.

CONCLUSION

QYYY effectively improves cardiac remodeling in hypertensive mice, potentially through inhibition of the PKM2-mediated glycolytic signaling pathway.