3-iodothyronamine inhibits apoptosis induced by myocardial ischemia reperfusion via the Akt/FoxO1 signaling pathway

Q: What are the key findings of this study?

3-iodothyronamine reduced myocardial infarct size and improved LVEF and LVFS after ischemia-reperfusion in rats via the Akt/FoxO1 pathway.

Q: What is the clinical evidence from this study?

Population: Myocardial ischemia reperfusion injury (n=46). Intervention: 3-iodothyronamine (T1AM) vs. Vehicle / Saline (I/R control) and Sham operation. Primary outcome: Myocardial infarct size, cardiac function (LVEF, LVFS), and cardiomyocyte apoptosis (p=<0.001).

Q: What does this research mean for the field?

Pretreatment with 3-iodothyronamine (T1AM) reduces myocardial infarct size, preserves cardiac function, and inhibits cardiomyocyte apoptosis after ischemia-reperfusion injury in rats via the Akt/FoxO1 pathway. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

Q: What question did this study set out to answer?

To investigate the protective effects of 3-iodothyronamine (T1AM) against myocardial ischemia reperfusion injury and determine its underlying molecular mechanisms.

Haiyan Zhou; Lili Mo; Niwen Huang; Changchao Zou; Chao Li; Muzhi Lin; Bei Zhang; Bo Wei; Ping Li; Xiaoyun Si; Jingjing Chen; Wei Li; Xingde Liu; Bailong Hu

doi:10.21037/atm-21-7041

February 1, 2022Annals of Translational MedicineOpen Access

3-iodothyronamine inhibits apoptosis induced by myocardial ischemia reperfusion via the Akt/FoxO1 signaling pathway

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Key result

3-iodothyronamine reduces infarct size and improves LVEF after myocardial ischemia-reperfusion via Akt/FoxO1 signaling.

P<0.001
n=46

Figures

Why the study?

The study investigated the potential effects of 3-iodothyronamine on myocardial ischemia reperfusion injury and the underlying molecular mechanisms.

Does 3-iodothyronamine (T1AM) reduce myocardial ischemia reperfusion injury in a rat model?

Key Points

To investigate the protective effects of 3-iodothyronamine (T1AM) against myocardial ischemia reperfusion injury and determine its underlying molecular mechanisms.
Initially randomized 16 adult male Sprague-Dawley rats into 4 groups given vehicle control, 25 mg/kg, 50 mg/kg, or 100 mg/kg T1AM to assess rectal body temperature over time.
Randomized 30 adult male Sprague-Dawley rats into sham, ischemia/reperfusion (I/R), and I/R + T1AM groups (n=10 per group), inducing ischemia by left anterior descending coronary artery occlusion for 0.5 hour followed by 3 hours of reperfusion.
Evaluated cardiac injury and performance via echocardiography, hemodynamics, TTC staining, transmission electron microscopy, serum biomarkers (LDH, CK, CK-MB), and Western blot analysis for apoptosis and Akt/FoxO1 pathway markers.
Intraperitoneal T1AM induced dose-dependent hypothermia (P<0.05), decreasing basal body temperature by 3–4 °C at 50 mg/kg before returning to baseline after 6–7 hours.
Pretreatment with 50 mg/kg T1AM significantly reduced myocardial infarct size (P<0.001), improved ejection fraction and fractional shortening (P<0.001), preserved mitochondrial ultrastructure, and lowered serum LDH, CK, and CK-MB levels compared with untreated I/R rats.
T1AM increased anti-apoptotic Bcl-2 and decreased pro-apoptotic Bax expression while significantly reducing Glut1, pFoxO1, and Akt, and elevating FoxO1 and PPARα levels.

Structured PICO

Does 3-iodothyronamine (T1AM) reduce myocardial ischemia reperfusion injury in a rat model?

P

Population

46 adult male Sprague-Dawley rats (200-250 g) divided into dose-response temperature assessment (n=16, followed for 6-7 hours) and myocardial ischemia-reperfusion injury experiments (n=30, 30 minutes LAD occlusion followed by 3-4 hours reperfusion).

I

Intervention

3-iodothyronamine (T1AM) pretreatment

C

Comparator

Sham operation or ischemia/reperfusion without T1AM (control vehicle: 60% DMSO and 40% saline)

O

Outcome

Myocardial injury evaluated by cardiac function, infarction size (TTC staining), and apoptosissurrogate

Main Result

p-value: p=<0.001

In a rat model, T1AM protects against myocardial ischemia-reperfusion injury by inhibiting apoptosis through the Akt/FoxO1 pathway.

Limitations

Preclinical animal model (Sprague-Dawley rats)
T1AM was administered only as an in vivo pretreatment
Only a single concentration of T1AM (50 mg/kg) was tested in the myocardial ischemia-reperfusion injury experiment

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Implication

Hypothesis-generating for T1AM cardioprotection; leaves open translation to human ischemia-reperfusion injury.

Abstract

Background: This study investigated the potential effects of 3-iodothyronamine (T1AM) on myocardial ischemia reperfusion injury (MIRI) and the underlying molecular mechanisms. Methods: A total of 16 adult male Sprague-Dawley rats were randomly divided into 4 groups and administered the following: control [60% dimethyl sulfoxide (DMSO) and 40% saline, pH 7.4], T1AM (25 mg/kg), T1AM (50 mg/kg), or T1AM (100 mg/kg). The rectal temperatures of the rats were measured at different time points. A further 30 adult male Sprague-Dawley rats were randomized and divided into the following 3 groups (n=10 in each group): sham operation, ischemia/reperfusion (I/R), and I/R + T1AM. In the I/R and I/R + T1AM groups, the left anterior descending (LAD) coronary artery of the rats were occluded for 0.5 hour to induce myocardial ischemia, followed by reperfusion for 3 hours in the I/R group. The electrocardiography (ECG), cardiac function, and 2,3,5-triphenyltetrazolium chloride (TTC) staining were examined in rats to evaluate the myocardial injury. The differences in the expression of apoptosis-related and Akt-FoxO1 signaling-related proteins were determined via Western blot. Results: This work verified that T1AM reduced the body temperature of rats in a dose-dependent manner. Additionally, T1AM improved cardiac function and decreased the infarction size caused by MIRI. T1AM reduced the expression of biochemical parameters and apoptosis of myocardial cells. In addition, after treatment with T1AM, the expression of Glut1, pFoxO1 and Akt were reduced, while the expression of FoxO1 and PPARα were increased significantly. Conclusions: Pretreatment of cardiomyocytes with T1AM inhibited apoptosis and protected against ischemia reperfusion injury via the Akt/FoxO1 signaling pathway.

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Cite This Study

Zhou et al. (2022) studied Myocardial ischemia reperfusion injury (n=46). 3-iodothyronamine (T1AM) vs. Vehicle / Saline (I/R control) and Sham operation was evaluated on Myocardial infarct size, cardiac function (LVEF, LVFS), and cardiomyocyte apoptosis (p=<0.001). 3-iodothyronamine reduced myocardial infarct size and improved LVEF and LVFS after ischemia-reperfusion in rats via the Akt/FoxO1 pathway.

synapsesocial.com/papers/6a73442e8c926c39f5c23d2c https://doi.org/10.21037/atm-21-7041

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3-iodothyronamine inhibits apoptosis induced by myocardial ischemia reperfusion via the Akt/FoxO1 signaling pathway

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Key Points

Structured PICO

Main Result

Limitations

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Implication

Abstract

Discussion

Cite This Study

3-iodothyronamine inhibits apoptosis induced by myocardial ischemia reperfusion via the Akt/FoxO1 signaling pathway

Figures

Key Points

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

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