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.

盐皮质激素受体阻滞剂依普利酮（Eperenone，EPL）可加速主动脉缩窄所致大鼠左室肥厚模型后负荷降低后左室肥厚向正常的逆转重构过程，改善左室向心性肥厚形态，并改善左室舒张功能障碍。组织学检查显示，与未处理的LV相比，EPL处理的LV沿着较小的心肌细胞直径和间质纤维化，以及较低的β/α-肌球蛋白重链比率和TGF-β1的mRNA表达。此外，EPL使未经治疗的LV中过度表达的盐皮质激素受体和血管紧张素-1 α受体的mRNA表达正常化。阻断盐皮质激素信号传导可能是后负荷减少（如主动脉瓣置换术）后残余LV肥大和舒张功能障碍的有效替代治疗。