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An In Vivo Estrogen Deficiency Mouse Model for Screening Exogenous Estrogen Treatments of Cardiovascular Dysfunction After Menopause
Published on: August 13, 2019
Hormone Replacement Therapy and Aging: A Potential Therapeutic Approach for Age-Related Oxidative Stress and Cardiac
Renáta Szabó1,2, Alexandra Hoffmann1, Denise Börzsei1
1Department of Physiology, Anatomy and Neuroscience, Faculty of Science and Informatics, University of Szeged, Szeged H-6726, Hungary.
Abstract:
Advanced age is an independent risk factor for cardiovascular diseases, which might be further exacerbated by estrogen deficiency. Hormone replacement therapy (HRT) decreases cardiovascular risks and events in postmenopausal women; however, its effects are not fully elucidated in older individuals. Thus, the aim of our study is to examine the impact of HRT on oxidant/antioxidant homeostasis and cardiac remodeling. In our experiment, control (fertile) and aging (~20-month-old) female Wistar rats were used. Aging rats were further divided into estrogen- (E2, 0.1 mg/kg/day per os) or raloxifene- (RAL, 1.0 mg/kg/day per os) treated subgroups. After 2 weeks of treatment, cardiac heme oxygenase (HO) activity, total glutathione (GSH) content, matrix metalloproteinase-2 (MMP-2) activity, and the concentrations of collagen type I and tissue inhibitor of metalloproteinase (TIMP-2), as well as the infarct size, were determined. The aging process significantly decreased the antioxidant HO activity and GSH content, altered the MMP-2/TIMP-2 signaling, and resulted in an excessive collagen accumulation, which culminated in cardiovascular injury. However, 2 weeks of either E2 or RAL treatment enhanced the antioxidant defense mechanisms and attenuated cardiac remodeling related to aging. Our findings clearly show that 2-week-long HRT is a potential intervention to bias successful cardiovascular aging via reducing oxidative damage and cardiovascular dysfunction.
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