Exploration of the metabolomic mechanisms of postmenopausal hypertension induced by low estrogen state

• Published in: eLife 2025-01, Vol.13
• Main Authors: Li, Yao, Xin, Hui, Lian, Zhexun, Zhang, Wei
• Format: Article
• Language: English
• Subjects: Animals; Blood Pressure; carbohydrate metabolism; Disease Models, Animal; Estrogens - metabolism; Female; Humans; Hypertension - metabolism; Medicine; Metabolome; Metabolomics; Ovariectomy; postmenopausal hypertension; Postmenopause; Rats; Rats, Sprague-Dawley; vascular remodeling
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/eLife.101701

Estrogen significantly impacts women's health, and postmenopausal hypertension is a common issue characterized by blood pressure fluctuations. Current control strategies for this condition are limited in efficacy, necessitating further research into the underlying mechanisms. Although metabolomics has been applied to study various diseases, its use in understanding postmenopausal hypertension is scarce. Therefore, an ovariectomized rat model was used to simulate postmenopausal conditions. Estrogen levels, blood pressure, and aortic tissue metabolomics were analyzed. Animal models were divided into Sham, OVX, and OVX +E groups. Serum estrogen levels, blood pressure measurements, and aortic tissue metabolomics analyses were performed using radioimmunoassay, UHPLC-Q-TOF, and bioinformatics techniques. Based on the above research content, we successfully established a correlation between low estrogen levels and postmenopausal hypertension in rats. Notable differences in blood pressure parameters and aortic tissue metabolites were observed across the experimental groups. Specifically, metabolites that were differentially expressed, particularly L-alpha-aminobutyric acid (L-AABA), showed potential as a biomarker for postmenopausal hypertension, potentially exerting a protective function through macrophage activation and vascular remodeling. Enrichment analysis revealed alterations in sugar metabolism pathways, such as the Warburg effect and glycolysis, indicating their involvement in postmenopausal hypertension. Overall, this current research provides insights into the metabolic changes associated with postmenopausal hypertension, highlighting the role of L-AABA and sugar metabolism reprogramming in aortic tissue. The findings suggest a potential link between low estrogen levels, macrophage function, and vascular remodeling in the pathogenesis of postmenopausal hypertension. Further investigations are needed to validate these findings and explore their clinical implications for postmenopausal women.