Effects of mineralocorticoid receptor blockade on reverse remodeling of the left ventricle after pressure load reduction

盐皮质激素受体阻断对压力负荷降低后左心室逆重塑的影响

• 批准号: 21591806
• 负责人: OZAWA Hideki
• 金额: $ 2.25万
• 依托单位: Osaka Medical College
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21591806/
• 关键词: 大動脈弁狭窄; 左心室肥大; 間質線維化; 大動脈弁置換術; リモデリング; アルドステロン系; ミネラロコルチコイド受容体拮抗; エプレレノン; 大動脈弁狭; 大動脈狭窄解除

Eplerenone(EPL), a mineralocorticoid receptor blocker, accelerates reverse remodeling process from hypertrophy to normal in the left ventricle(LV) after after-load reduction in rat model of LV hypertrophy induced by transverse aortic constriction.EPL ameliorated concentric hypertrophic morphology and impaired LV diastolic dysfunction remaining in the untreated LV. Histological examination showed less diameter of cardiomyocytes and interstitial fibrosis in EPL-treated LV along with less mRNA expression of β/α-myosin heavy chain ratio and TGF-β1 when compared to un-treated LV. Moreover, EPL normalized the mRNA expression of mineralocorticoid receptor and angiotensin-1α-receptor that were over-expressed in the untreated LV.Blocking mineralocorticoid signaling may be an effective alternate treatment for residual LV hypertrophy and diastolic dysfunction after after-load reduction, such as aortic valve replacement.

eplerenone（EPL）是一种矿物皮质激素受体阻滞剂，在横向主动脉收缩诱导的LV肥大大鼠模型后，在左心室（LV）中加速了从肥大到正常的反向重塑过程。组织学检查表明，与未经处理的LV相比，EPL处理的LV中心肌细胞和间质纤维化的直径较小，β/α-乳糖蛋白重链比和TGF-β1的mRNA表达较少。此外，EPL使矿物皮质受体受体和血管紧张素-1α受体的mRNA表达在未经处理的LV中过表达。块状矿体皮质激素信号传导可能是残留LV肥大和舒张功能障碍后的有效替代治疗方法，后负载减少后负载减少了Atrortic plestic pleplace胶剂。