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

2011 Fiscal Year Final Research Report

• Project/Area Number: 21591806
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Thoracic surgery
• Research Institution: Osaka Medical College
• Principal Investigator: OZAWA Hideki 大阪医科大学, 医学部, 助教 (20277156)
• Co-Investigator(Kenkyū-buntansha): NEMOTO Shintarou 大阪医科大学, 医学部, 准教授 (20237811) ; TAKAI Shinji 大阪医科大学, 医学部, 准教授 (80288703) ; HOSHIGA Masaaki 大阪医科大学, 医学部, 助教 (90309154)
• Co-Investigator(Renkei-kenkyūsha): HAMORI Kan 大阪医科大学, 医学部, 助教 (90581207) ; SASAKI Tomoyasu 大阪医科大学, 医学部 (10411365)
• Project Period (FY): 2009 – 2011
• Keywords: 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

Research Abstract

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.