Ganoderma lucidum spore oil and physiological choline supplementation attenuated cardiac hypertrophy, fibrosis, and ejection fraction decline in a mouse model of pressure overload-induced heart failure.
Does Ganoderma lucidum spore oil or choline supplementation prevent pressure overload-induced heart failure with reduced ejection fraction in a mouse model?
Myocardial choline preservation mediates the cardioprotective effects of Ganoderma lucidum spore oil against pressure overload-induced HFrEF, defining a novel metabolic-signaling axis.
Abstract Chronic pressure overload, caused by hypertension or aortic stenosis, drives maladaptive cardiac remodeling from concentric hypertrophy to eccentric hypertrophy and heart failure with reduced ejection fraction (HFrEF). Metabolic dysregulation is central to this process and its resultant dysfunction. Ganoderma lucidum spore oil (GSO) exhibits cardioprotective properties; however, the underlying mechanisms and key mediators remain unclear. This study aimed to determine whether GSO ameliorates pressure overload-induced HFrEF by modulating myocardial metabolism, and to identify specific metabolites mediating its effects. Male C57BL/6J mice underwent transverse aortic constriction (TAC) to induce progressive remodeling. Mice were randomized to sham operation (SHAM), TAC, TAC+GSO (100 mg/kg/day), or TAC+physiological dose choline (7 mg/kg/day), according to the experimental design, for up to 8 weeks. Left ventricular geometry, function (echocardiography and strain imaging), myocardial injury (cardiac troponin T assay and histology), bioenergetics (ATP and actomyosin MgATPase), Ca²⁺ handling, electrical activity (electrocardiogram and ion channel expression), and global metabolism (untargeted metabolomics) were assessed. GSO attenuated hypertrophy, fibrosis, and ejection fraction (EF) decline across the concentric-eccentric transition, and restored myocardial choline depleted by TAC. Low-dose choline supplementation reproduced the benefits of GSO on systolic and diastolic function, deformation indices, myocardial structure, conduction stability, ATP content, Ca²⁺ handling, and MgATPase activity. Transcriptomics and pathway analysis (RNA sequencing and Ingenuity Pathway Analysis) mapped signaling changes. Mechanism study verified that both interventions suppressed pro-hypertrophic signaling by reducing phosphorylation along the RAF/MEK/ERK cascade. Myocardial choline preservation is a central mechanism of GSO‑mediated cardioprotection against pressure overload-induced HFrEF. Physiological choline restoration recapitulates these benefits, defining a novel metabolic–signaling axis with translational potential in hypertensive heart disease.
Tan et al. (Mon,) conducted a other in Pressure overload-induced heart failure with reduced ejection fraction (HFrEF). Ganoderma lucidum spore oil (GSO) and Choline vs. Sham operation or TAC with vehicle (0.9% NaCl) was evaluated on Left ventricular geometry, function (ejection fraction), and myocardial remodeling. Ganoderma lucidum spore oil and physiological choline supplementation attenuated cardiac hypertrophy, fibrosis, and ejection fraction decline in a mouse model of pressure overload-induced heart failure.