Long-term thyroid hormone administration reshapes left ventricular chamber and improves cardiac function after myocardial infarction in rats

Pantos, Constantinos; Mourouzis, Iordanis; Markakis, Konstantinos; Tsagoulis, N.; Panagiotou, Matthew; Cokkinos, Dennis V.

doi:10.1007/s00395-008-0697-0

Cited by 113 publications

(110 citation statements)

References 42 publications

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“…On the other hand, our data indicate that Low-T3S persistence favors cardiac disease evolution and confirmed that, to be effective on adverse remodeling, the timing of Low-T3S correction should encompass the regenerative window that is lost in the late postischemic phase (48). In accordance, T3 replacement initiated 1 wk after MI improved ventricular performance without reversing cardiac remodeling (28), whereas THs administered early after I/R improved cardiac function and prevented LV chamber remodeling (17,30,31,47). However, the effectiveness of THs on cardiac geometry and function has also been reported in rats with old myocardial infarction (49).…”

Section: Disclosuresupporting

confidence: 76%

“…Furthermore, clinical studies have shown that levels of T3 have a positive correlation with ejection fraction (EF%) in ST-elevation myocardial infarction (STEMI) patients at 48 h from the index event (22). Consistently, treatment of Low-T3S exerts cardioprotective effects in both humans and animal models and may be a novel option for treatment of cardiac disease (23)(24)(25)(26)(27)(28)(29)(30).…”

Section: Experimental Protocolmentioning

confidence: 92%

“…ECG recordings were continuously acquired at a 2-kHz sampling rate (ML135 PowerLab/8SP equipped with ML135 Dual Bio Amp and MLA0112 ECG Lead Switch Box, ADI Instruments) during surgery up to 60 min after LAD occlusion. Arrhythmias were classified according to the Lambeth Conventions (30,33). A scoring system (31) was used to classify their severity, as detailed in the supplementary materials.…”

Section: Echocardiography Studymentioning

confidence: 99%

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Early and Short-term Triiodothyronine Supplementation Prevents Adverse Postischemic Cardiac Remodeling: Role of Transforming Growth Factor-β1 and Antifibrotic miRNA Signaling

Nicolini

Forini

Kusmic

et al. 2015

Mol Med

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Activation of transforming growth factor (TGF)-β1 signaling in the ischemia/reperfusion (I/R) injured myocardium leads to dysregulation of miR-29-30-133, favoring the profibrotic process that leads to adverse cardiac remodeling (CR). We have previously shown that timely correction of the postischemic low-T3 syndrome (Low-T3S) exerts antifibrotic effects, but the underlying molecular players are still unknown. Here we hypothesize that a prompt, short-term infusion of T3 in a rat model of post I/R Low-T3S could hamper the early activation of the TGFβ1-dependent profibrotic cascade to confer long-lasting cardioprotection against adverse CR. Twenty-four hours after I/R, rats that developed the Low-T3S were randomly assigned to receive a 48-h infusion of 6 μg/kg/d T3 (I/R-L+T3) or saline (I/R-L) and sacrificed at 3 or 14 d post-I/R. Three days post-I/R, Low-T3S correction favored functional cardiac recovery. This effect was paralleled by a drop in TGFβ1 and increased miR-133a, miR-30c and miR-29c in the infarcted myocardium. Consistently, connective transforming growth factor (CTGF) and matrix metalloproteinase-2 (MMP-2), validated targets of the above miRNAs, were significantly reduced. Fourteen days post-I/R, the I/R-L+T3 rats presented a significant reduction of scar size with a better preservation of cardiac performance and LV chamber geometry. At this time, TGFβ1 and miR-29c levels were in the normal range in both groups, whereas miR-30c-133a, MMP-2 and CTGF remained significantly altered in the I/R group. In conclusion, the antifibrotic effect exerted by T3 in the early phase of postischemic wound healing triggers a persistent cardioprotective response that hampers the progression of heart dysfunction and adverse CR.

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Section: Disclosuresupporting

confidence: 76%

Section: Experimental Protocolmentioning

confidence: 92%

Section: Echocardiography Studymentioning

confidence: 99%

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Early and Short-term Triiodothyronine Supplementation Prevents Adverse Postischemic Cardiac Remodeling: Role of Transforming Growth Factor-β1 and Antifibrotic miRNA Signaling

Nicolini

Forini

Kusmic

et al. 2015

Mol Med

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“…5 It is likely that reexpression of the fetal gene program in the overloaded ventricle, a common feature of cardiac disease, is enhanced by low tissue TH levels. Pantos and colleagues [51][52][53][54][55] have published numerous animal studies on the effects of THs on the heart, particularly during ischemia or MI. They have shown that short-and long-term T3ϩT4 treatment of rats with MI leads to improved LV function and remodeling.…”

Section: Th Metabolism During the Early Post-mi Phasementioning

confidence: 99%

Thyroid Replacement Therapy and Heart Failure

2010

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“…Las áreas diastólicas (AD) y sistólicas (AS) del VI se midieron en el modo bidimensional, por medio de planimetría, en dos líneas paraesternales: eje largo y eje menor. El índice de esfericidad se determinó al dividir el área diastólica obtenida en el eje mayor por el área diastólica obtenida en el eje menor, y el índice de estrés de la pared ventricular izquierda se determinó por la fórmula: (área diastólica/2 x HDVI) 21 . La función sistólica del VI se evaluó al calcularse la fracción de variación de área (FVA=AD-AS/AD x 100) 20 .…”

Section: Estudio Ecocardiográficounclassified

Relação entre a esfericidade, a função ventricular e o tamanho do infarto em ratos

Minicucci

Azevedo

Matsubara

et al. 2010

Arq. Bras. Cardiol.

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Artículo recibido el 16/04/09; revisado recibido el 01/10/09; aceptado el 07/10/09. ResumenFundamento: La esfericidad del ventrículo izquierdo (VI) es factor asociado a la disfunción ventricular, sin embargo no está bien caracterizada en el modelo de ratones infartados.Objetivo: Analizar la relación entre el índice de esfericidad, la función ventricular y el área infartada en el modelo experimental en ratones.Métodos: Seis meses tras el infarto (IAM, n = 33) o cirugía simulada (SHAM, n = 18), los animales fueron sometidos a ecocardiograma. El índice de esfericidad se obtuvo mediante la razón entre las áreas diastólicas en los ejes mayor y menor del VI. proceso resulta en mayor prevalencia de ruptura ventricular, aneurismas y arritmias malignas. Adicionalmente, la remodelación está relacionada a la aparición y la progresión de la disfunción ventricular [1][2][3][4][5][6][7] . Debemos tener en cuenta que una de las estrategias más utilizadas para el estudio de la remodelación resultante de la oclusión coronaria es el modelo del infarto experimental en el ratón. Entre otros factores, la utilización de este modelo tiene lugar en consecuencia de la similitud entre las alteraciones fisiopatológicas que se producen en los ratones y humanos tras el infarto 8,9 . En los últimos años, el índice de esfericidad, obtenido por medio del ecocardiograma, se viene utilizando para la evaluación de la remodelación ventricular secundaria a diferentes etiologías [10][11][12][13][14][15][16] . Sin embargo, la utilización de este índice en el modelo de ratones infartados no es común, por tanto, no está caracterizada. Así, el objetivo de este estudio fue analizar la relación entre el índice de esfericidad, la función ventricular y el tamaño de la lesión isquémica en el modelo del infarto experimental en ratones. Resultados IntroducciónTras el infarto agudo de miocardio (IAM) pueden producirse alteraciones de la arquitectura ventricular implicando tanto la región infartada como la no infartada. Actualmente, prevalece el concepto de que las alteraciones morfológicas ya sean consecuencia de alteraciones celulares, moleculares e intersticiales cardíacas que se produzcan en respuesta a determinada agresión. El conjunto de estas adaptaciones, que se detectan clínicamente por alteraciones en la composición, masa, volumen y geometría cardíaca, se lo designa remodelación cardíaca [1][2][3][4] . La presencia y la intensidad de la remodelación están directamente asociadas al peor pronóstico, ya que este 627

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Long-term thyroid hormone administration reshapes left ventricular chamber and improves cardiac function after myocardial infarction in rats

Cited by 113 publications

References 42 publications

Early and Short-term Triiodothyronine Supplementation Prevents Adverse Postischemic Cardiac Remodeling: Role of Transforming Growth Factor-β1 and Antifibrotic miRNA Signaling

Early and Short-term Triiodothyronine Supplementation Prevents Adverse Postischemic Cardiac Remodeling: Role of Transforming Growth Factor-β1 and Antifibrotic miRNA Signaling

Thyroid Replacement Therapy and Heart Failure

Relação entre a esfericidade, a função ventricular e o tamanho do infarto em ratos

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