| Immediate mineralocorticoid receptor blockade improves myocardial infarct healing by modulation of the inflammatory response. | |
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MedLine Citation:
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PMID: 18299485 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Mineralocorticoid receptor (MR) blockade reduces morbidity and mortality after acute myocardial infarction; however, the underlying mechanisms are still under investigation. This study examined whether MR antagonism promotes healing of the infarcted myocardium. Starting immediately after coronary ligation, male Wistar rats were treated with the selective MR antagonist eplerenone (100 mg/kg per day by gavage) or placebo for 2 to 7 days. At 7 days, eplerenone therapy versus placebo significantly reduced thinning and dilatation of the infarcted wall, improved left ventricular function, and enhanced neovessel formation in the injured myocardium. At 2 days, eplerenone-treated rats displayed lower plasma corticosterone levels, higher circulating blood monocytes, and more macrophages infiltrating the infarcted myocardium. MR blockade led to a transient upregulation (at days 2 and 3 but not at day 7) of monocyte chemoattractant protein-1, tumor necrosis factor-alpha, interleukin-1beta, interleukin-6, interleukin-10, and interleukin-4 and an increase in factor XIIIa protein expression in the healing myocardium. Prevention of macrophage accumulation into the infarct zone by treatment with liposome-encapsulated clodronate almost abrogated the protein expression of factor XIIIa and the beneficial effects of eplerenone on infarct expansion. In conclusion, selective MR blockade immediately after myocardial infarction accelerated macrophage infiltration and transiently increased the expression of healing promoting cytokines and factor XIIIa in the injured myocardium resulting in enhanced infarct neovascularization and reduced early LV dilation and dysfunction. |
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Authors:
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Daniela Fraccarollo; Paolo Galuppo; Susanne Schraut; Susanne Kneitz; Nico van Rooijen; Georg Ertl; Johann Bauersachs |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2008-02-25 |
Journal Detail:
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Title: Hypertension Volume: 51 ISSN: 1524-4563 ISO Abbreviation: Hypertension Publication Date: 2008 Apr |
Date Detail:
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Created Date: 2008-03-21 Completed Date: 2008-04-16 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7906255 Medline TA: Hypertension Country: United States |
Other Details:
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Languages: eng Pagination: 905-14 Citation Subset: IM |
Affiliation:
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Medizinische Klinik und Poliklinik I, Julius-Maximilians-Universität Würzburg, Würzburg, Germany. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Aldosterone
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blood Aldosterone Antagonists / pharmacology Animals Clodronic Acid / pharmacology* Collagen / metabolism Cytokines / metabolism Factor XIIIa / genetics Heart Failure / drug therapy, immunology, pathology Humans Male Monocytes / drug effects, immunology, metabolism Myocardial Infarction / drug therapy*, immunology*, pathology Myocarditis / drug therapy, pathology Myocardium / metabolism, pathology Neovascularization, Physiologic / drug effects RNA, Messenger / metabolism Rats Rats, Wistar Receptors, Mineralocorticoid / antagonists & inhibitors* Spironolactone / analogs & derivatives, pharmacology Ventricular Function, Left / drug effects Wound Healing / drug effects* |
| Chemical | |
Reg. No./Substance:
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0/Aldosterone Antagonists; 0/Cytokines; 0/RNA, Messenger; 0/Receptors, Mineralocorticoid; 0/eplerenone; 10596-23-3/Clodronic Acid; 52-01-7/Spironolactone; 52-39-1/Aldosterone; 9007-34-5/Collagen; EC 2.3.2.13/Factor XIIIa |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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