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In vitro Assessment of Myocardial Protection following Hypothermia-Preconditioning in a Human Cardiac Myocytes Model
Published on: October 27, 2020
Hyperthyroid hearts display a phenotype of cardioprotection against ischemic stress: a possible involvement of heat
C Pantos1, V Malliopoulou, I Mourouzis
1Department of Pharmacology, University of Athens. cpantos@cc.uoa.gr
Insights
Long-term thyroxin treatment enhances heart protection against ischemic stress by increasing Heat Shock Protein 70 (HSP70) expression. This suggests HSP70 plays a key role in thyroid hormone-induced cardioprotection.
Area of Science:
- Cardiovascular Physiology
- Molecular Biology
- Endocrinology
Background:
- Hyperthyroid hearts exhibit cardioprotection against ischemia, but mechanisms are unclear.
- Heat Shock Protein 70 (HSP70) is a stress-responsive chaperone enhancing cell survival.
- Thyroid hormones may influence myocardial stress resilience via HSP70.
Purpose of the Study:
- To investigate the relationship between HSP70 and thyroid hormone-induced cardioprotection.
- To determine if long-term thyroxin administration alters HSP70 expression and myocardial tolerance to ischemia/reperfusion (I/R).
Main Methods:
- Wistar rats received thyroxin for 4 or 14 days.
- Isolated hearts underwent 20 min ischemia followed by 45 min reperfusion (I/R).
- Myocardial HSP70 levels and oxidative stress (MDA) were measured; functional recovery post-I/R was assessed.
Main Results:
- Long-term (14-day) thyroxin treatment significantly increased myocardial HSP70 levels (1.85-fold) compared to controls.
- Short-term (4-day) thyroxin treatment did not alter HSP70 levels.
- Hearts from long-term treated rats showed significantly improved functional recovery after I/R, unlike short-term treated hearts.
- Increased oxidative stress (MDA) was noted in long-term treated hearts.
Conclusions:
- Long-term thyroxin administration confers myocardial tolerance to I/R.
- Enhanced HSP70 expression in the myocardium likely contributes to this cardioprotective effect.
- Thyroid hormone-induced cardioprotection is time-dependent and associated with HSP70 upregulation.
Abstract:
Hyperthyroid hearts are shown to display a phenotype of cardioprotection against ischemic stress, but the underlying signaling mechanisms remain largely unknown. The present study investigated the possible relation of HSP70 to the thyroid hormone induced cardioprotection. HSP70 is a redox-regulated molecular chaperone, and enhances cell survival under stress. Thyroxin (25 microg/100 g body weight) was administered to Wistar male rats for four days (THYR-4d) and two weeks (THYR-14d), respectively, while untreated animals served as controls (CON-4d, CON-14d). Isolated hearts from control and thyroxin treated rats were subjected to 20 min zero-flow ischemia followed by 45 min of reperfusion (I/R). The amount of HSP70 in the myocardium for THYR-14d was 1.85 times the levels of CON-14d (p < 0.05). The levels of HSP70 expression were no different between THYR-4d and CON-4d, p > 0.05. This was only accompanied by an increase in MDA levels (used as an index of oxidative stress) in THYR-14d compared to untreated hearts. These changes corresponded to a differential response of the heart to I/R; post-ischemic recovery of function was significantly increased in THYR-14d compared to CON-14d, and was no different between the THYR-4d and CON-4d hearts. In conclusion, long-term thyroxin administration results in increased tolerance of the myocardium to I/R and enhances the expression of HSP70 which may, at least in part, account for this response.
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