Thyroid hormone attenuates cardiac remodeling and improves hemodynamics early after acute myocardial infarction in rats

Pantos, Constantinos; Mourouzis, Iordanis; Markakis, Konstantinos; Dimopoulos, Antonios; Xinaris, Christodoulos; Kokkinos, Alexandros; Panagiotou, Matthew; Cokkinos, Dennis V.

doi:10.1016/j.ejcts.2007.05.004

Cited by 91 publications

(70 citation statements)

References 23 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).…”

Section: Disclosuresupporting

confidence: 62%

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: 62%

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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“…These changes in the expression of cardiac genes are also characteristic of pathological cardiac remodeling after myocardial infarction (18) and lead to decreased contractility of the myocardium, inhibited Ca 2+ transport, a worsened diastolic function, calcium overload, myocardial stunning and reperfusion injury. Animal experiments also show that thyroid hormone replacement treatment can reverse the changes in the shape and geometry of cardiac myocytes that occur after AMI (19). In addition, thyroid hormones are powerful regulators of vasculature in the adult myocardium; therefore, a low fT3 state would inhibit neovascularization in cardiac tissue after AMI, which would accelerate cardiac pathologic remodeling and heart failure (20).…”

Section: Discussionmentioning

confidence: 99%

A Low fT3 Level as a Prognostic Marker in Patients with Acute Myocardial Infarctions

et al. 2012

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Objective To investigate the association between low free triiodothyronine (fT3) levels and the severity and prognosis of patients with acute myocardial infarction. Methods A total of 501 patients with acute myocardial infarctions were enrolled in our study. The circulating levels of thyroid hormones and clinical parameters were assayed. The patients were categorized into either the low fT3 group or the normal fT3 group according to the fT3 level on admission. All patients underwent a follow-up for 10±2 months for mortality from any cause and the occurrence of any adverse major cardiac events (MACE). Results There were 171 patients in the low fT3 group (fT3<3.5 pmol/L) and 330 patients in the normal fT3 group (! 3.5 pmol/L). During the follow-up period, 33 patients died (6.6%) and the overall survival rates were 86.0% and 97.3% in patients with a low fT3 level and a normal fT3 level, respectively. The rates of MACE were 66.7% and 45.5% in the patients with and those without low fT3 levels, respectively. Using a multivariable Cox proportional hazards model, the fT3 level was found to be the most important predictor of cumulative death and MACE (hazard ratio [HR] for death: 0.142, p<0.001 and HR for major adverse cardiac events: 0.748, p=0.007). A Kaplan-Meier analysis revealed that those patients with low fT3 levels had higher rates of MACE and death. Conclusion A low fT3 level, a common phenomenon in patients with acute myocardial infarctions, is a strong predictor of short-term and long-term poor prognoses in patients with acute myocardial infarctions.

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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%

“…They have shown that short-and long-term T3ϩT4 treatment of rats with MI leads to improved LV function and remodeling. 53,54 However, remodeling data were limited to echocardiographs and measurement of infarct size with no tissue structure analyses of spared myocardium. Importantly, the Pantos group has not observed any TH treatment-related changes in infarct scar remodeling.…”

Section: Th Metabolism During the Early Post-mi Phasementioning

confidence: 99%

Thyroid Replacement Therapy and Heart Failure

2010

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Thyroid hormone attenuates cardiac remodeling and improves hemodynamics early after acute myocardial infarction in rats

Abstract: Thyroid hormone administration early after infarction attenuates cardiac remodeling and significantly improves myocardial performance.

Cited by 91 publications

References 23 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

A Low fT3 Level as a Prognostic Marker in Patients with Acute Myocardial Infarctions

Thyroid Replacement Therapy and Heart Failure

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