Up-regulation of heme oxygenase-1 after infarct initiation reduces mortality, infarct size and left ventricular remodeling: experimental evidence and proof of conceptReport as inadecuate




Up-regulation of heme oxygenase-1 after infarct initiation reduces mortality, infarct size and left ventricular remodeling: experimental evidence and proof of concept - Download this document for free, or read online. Document in PDF available to download.

Journal of Translational Medicine

, 12:89

Cardiovascular, Metabolic and Lipoprotein Translation

Abstract

BackgroundUp-regulation of HO-1 by genetic manipulation or pharmacological pre-treatment has been reported to provide benefits in several animal models of myocardial infarction MI. However, its efficacy following MI initiation as in clinical reality remains to be tested. Therefore, this study investigated whether HO-1 over-expression, by cobalt protoporphyrin CoPP administered after LAD ligation, is still able to improve functional and structural changes in left ventricle LV in a rat model of 4-week MI.

MethodsA total of 144 adult male Wistar rats were subjected to either left anterior coronary artery ligation or sham-operation. The effect of CoPP treatment 5 mg-kg i.p. at the end of the surgical session and, then, once a week for 4 weeks was evaluated on the basis of survival, electro- and echocardiography, plasma levels of B-type natriuretic peptide BNP, endothelin-1 and prostaglandin E2, coronary microvascular reactivity, MI size, LV wall thickness and vascularity. Besides, the expression of HO-1 and connexin-43 in different LV territories was assessed by western blot analysis and immunohistochemistry, respectively.

ResultsCoPP induced an increased expression of HO-1 protein with >16 h delay. CoPP treatment significantly reduced mortality, MI size, BNP concentration, ECG alterations, LV dysfunction, microvascular constriction, capillary rarefaction and restored connexin-43 expression as compared to untreated MI. These functional and structural changes were paralleled by increased HO-1 expression in all LV territories. HO activity inhibition by tin-mesoporphyrin abolished the differences between CoPP-treated and untreated MI animals.

ConclusionsThis is the first report demonstrating the putative role of pharmacological induction of HO-1 following coronary occlusion to benefit infarcted and remote territories, leading to better cardiac function in a 4-week MI outcome.

KeywordsMyocardial infarction Coronary microvascular reactivity Left ventricular vascularity Ventricular remodeling Connexin-43 Cobalt protoporphyrin IX Tin mesoporphyrin Electronic supplementary materialThe online version of this article doi:10.1186-1479-5876-12-89 contains supplementary material, which is available to authorized users.

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Author: Claudia Kusmic - Cristina Barsanti - Marco Matteucci - Nicoletta Vesentini - Gualtiero Pelosi - Nader G Abraham - Antonio 

Source: https://link.springer.com/







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