BASIC RESEARCH

Effects of eplerenone on transcriptional factors and mRNA expression related to cardiac remodelling after myocardial infarction

S Enomoto¹, M Yoshiyama¹, T Omura¹, R Matsumoto¹, T Kusuyama¹, S Kim², Y Izumi², K Akioka¹, H Iwao², K Takeuchi¹, J Yoshikawa¹

¹ Department of Internal Medicine and Cardiology, Osaka City University Medical School, Osaka, Japan
² Department of Pharmacology, Osaka City University Medical School, Osaka, Japan

Correspondence to:
Dr Minoru Yoshiyama
Department of Internal Medicine and Cardiology, Osaka City University Medical School, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan; yoshiyama{at}med.osaka-cu.ac.jp

Objective: To examine the effects of eplerenone, a selective aldosterone blocker, on cardiac function after myocardial infarction (MI) and myocardial remodelling related transcriptional factors and mRNA expression in non-infarcted myocardium.

Methods: MI was induced by ligation of the coronary artery in Wistar rats. Rats were randomly assigned to a vehicle treated group or an eplerenone treated group (100 mg/kg/day).

Results: At four weeks after MI, left ventricular (LV) end diastolic pressure, LV weight, and LV end diastolic dimension were increased in MI rats. Eplerenone significantly reduced the increase in LV end diastolic pressure, LV weight, and LV end diastolic dimension. In the MI rats the decreased ejection fraction indicated systolic dysfunction and the increased E wave to A wave ratio and E deceleration rate indicated diastolic dysfunction. Eplerenone significantly attenuated this systolic and diastolic dysfunction. Myocardial interstitial fibrosis, transcriptional activities of activator protein 1 and nuclear factor B, and mRNA expression of monocyte chemoattractant protein 1, plasminogen activator inhibitor 1, atrial natriuretic peptide, brain natriuretic peptide, and collagen types I and III were significantly increased at four weeks after MI. Eplerenone significantly attenuated interstitial fibrosis and suppressed transcriptional activity and mRNA expression of these genes.

Conclusions: When administered after MI, eplerenone prevents cardiac remodelling accompanied by systolic and diastolic dysfunction and inhibits abnormal myocardial transcriptional activities and gene expression.

Abbreviations: ACEI, angiotensin converting enzyme inhibitor; ANP, atrial natriuretic peptide; AP-1, activator protein 1; ARB, angiotensin II type 1 receptor blocker; BNP, brain natriuretic peptide; EPHESUS, eplerenone post-acute myocardial infarction heart failure efficacy and survival study; LV, left ventricular; LVEF, left ventricular ejection fraction; MCP-1, monocyte chemoattractant protein 1; MI, myocardial infarction; NF, nuclear factor; PAI-1, plasminogen activator inhibitor 1; RALES, randomised aldactone evaluation study

Keywords: aldosterone; eplerenone; myocardial infarction; cardiac remodelling; monocyte chemoattractant protein 1; plasminogen activator inhibitor 1

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