Hyperthyroid Hearts Display a Phenotype of Cardioprotection Against Ischemic Stress: A Possible Involvement of Heat Shock Protein 70

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.

Interaction of Cardiovascular Risk Factors with Myocardial Ischemia/Reperfusion Injury, Preconditioning, and Postconditioning

“…For example, there is evidence that in hyperthyroid rat myocardium, increased phosphorylation of PKC-and decreased phosphorylation of p38 MAP kinase are present (Pantos et al, 2001), whereas in isolated rat cardiomyocytes, subacute (24-h) application of T3 is associated with activation of the prosurvival kinase Akt (Kuzman et al, 2005). The 70-and 27-kDs heat shock proteins (HSP70 and HSP27) associated with late preconditioning have been shown to be up-regulated in the hyperthyroid heart (Pantos et al, 2006), although a causal relationship between their induction and the cardioprotected phenotype in hyperthyroid hypertrophy has not been conclusively demonstrated.…”

Time-dependent changes in the expression of thyroid hormone receptor α1 in the myocardium after acute myocardial infarction: possible implications in cardiac remodelling

“…A non-ejecting isolated rat heart preparation was perfused at a constant flow according to the Langendorff technique (19,20). An intraventricular balloon allowed measurement of contractility under isovolumic conditions.…”

Heart Failure and Protein Quality Control

“…The small HSPs play important chaperone and protective roles in the heart and the nomenclature, and classification of the members in the family has recently been reviewed in detail. 7 They are abundant in cardiomyocytes and are upregulated during cardiac stress and disease, 8,9 with a single member, ␣-B crystallin (CryAB), making up as much as 3% of the total soluble protein mass. CryAB binds both desmin and cytoplasmic actin and possesses molecular chaperone function in vitro.…”