Department of Biomedical Engineering, Vanderbilt University, Nashville, Tennessee.
Department of Orthopaedic Surgery, Vanderbilt University Medical Center, Nashville, Tennessee.
Am J Physiol Heart Circ Physiol. 2022 Jun 1;322(6):H1080-H1085. doi: 10.1152/ajpheart.00157.2022. Epub 2022 Apr 29.
Postmenopausal women tend to have worse cardiovascular outcomes in a manner that is associated with osteoporosis severity. In this study, we performed the first evaluation of the left ventricle and aortic valve phenotype of ovariectomized mice aged on Western diet to 1 yr. Disease was monitored in vivo using echocardiography and dual X-ray absorptiometry imaging and ex vivo using quantitative histological and immunostaining analysis. Mice had decreased bone mineral density in response to ovariectomy and increased fat mass in response to Western diet. Ovariectomized mice had a significantly increased left ventricle mass compared with control animals, absent of fibrosis. There was a slight increase in aortic valve peak velocity but no change in mean pressure gradient across the valve in the ovariectomy group. There was no evidence of leaflet hypertrophy, fibrosis, or calcification. This model of ovariectomy may present a novel method of studying left ventricle hypertrophy in female populations but does not have a phenotype for the study of aortic stenosis. This is particularly useful as it does not require genetic manipulation or drug treatment and more faithfully mimics aging, high-cholesterol diet, and postmenopausal osteoporosis that many female patients experience potentially resulting in a more translatable disease model. This article uses in vivo and ex vivo analysis to track the development of osteoporosis and left heart cardiovascular disease in an aged, high-cholesterol diet, mouse ovariectomy model. Mice develop early left ventricle hypertrophy without concurrent fibrosis or aortic valve stenosis. These findings allow for a new model of the study of left ventricle hypertrophy in postmenopausal osteoporosis that more closely mimics the natural progression of disease in female patients.
绝经后女性的心血管结局往往更差，这种情况与骨质疏松症的严重程度有关。在这项研究中，我们首次评估了在西方饮食下 1 年的去卵巢小鼠的左心室和主动脉瓣表型。通过超声心动图和双 X 射线吸收测定成像在体内以及通过定量组织学和免疫染色分析在体外监测疾病。去卵巢小鼠的骨密度降低，对西方饮食的反应脂肪量增加。与对照动物相比，去卵巢小鼠的左心室质量明显增加，但没有纤维化。主动脉瓣峰值速度略有增加，但瓣上平均压力梯度没有变化。没有瓣叶肥大、纤维化或钙化的证据。这种去卵巢模型可能为研究女性人群中的左心室肥厚提供了一种新方法，但不具有研究主动脉瓣狭窄的表型。这尤其有用，因为它不需要遗传操作或药物治疗，并且更忠实地模拟了许多女性患者经历的衰老、高胆固醇饮食和绝经后骨质疏松症，从而产生更具转化性的疾病模型。本文使用体内和体外分析来追踪在年龄较大、高胆固醇饮食、小鼠去卵巢模型中骨质疏松症和左心心血管疾病的发展。小鼠出现早期左心室肥厚，而没有同时发生纤维化或主动脉瓣狭窄。这些发现为绝经后骨质疏松症左心室肥厚的研究提供了一种新模型，更能模拟女性患者疾病的自然进展。
