A Novel Insight into Postmenopausal Hypercholesterolemia: Carnitine as a Key Player

<b><i>Background:</i></b> Postmenopausal women (post-MW) are at a heightened risk of cardiovascular diseases, including hypercholesterolemia. This study aimed to investigate metabolomic variations to identify potential markers and targets for postmenopausal hypercholesterolemia. <b><i>Methods:</i></b> Sixty-two female volunteers aged 40-65 were recruited for this study. Metabolomic analysis using the Ultra-Performance Liquid Chromatography Quadrupole Orbitrap Mass Spectrometry (UPLC-Q-Orbitrap MS) platform was conducted to investigate changes in endogenous substances in premenopause (<i>n</i> = 25) and postmenopause (<i>n</i> = 37) women. Following ovariectomy surgery, menopausal mice were monitored for changes in their biomarker levels, and the integrity of the large artery walls in each treatment group was observed through hematoxylin and eosin staining. <i>In vitro</i> cellular models were utilized to assess variations in lipid metabolism, reactive oxygen species (ROS) levels, and changes in the levels of superoxide dismutase and glutathione peroxidase enzymes in different cell groups postintervention using Western blot analysis. <b><i>Results:</i></b> Treatment with carnitine in postmenopausal mouse models led to increased plasma cholesterol and carnitine levels, as well as indicators of arterial sclerosis. In HepG2 cells, carnitine treatment resulted in heightened lipid levels, elevated ROS production, and decreased antioxidant enzyme levels. <b><i>Conclusions:</i></b> The findings suggest that carnitine may serve as a potential risk marker or therapeutic target for postmenopausal hypercholesterolemia. This study provides valuable insights into cardiovascular conditions in post-MW and offers new avenues for therapeutic interventions. Continued research in this area is crucial to enhance our understanding of cardiovascular diseases in post-MW and to explore additional treatment options.