| First Author | Pape J | Year | 2022 |
| Journal | Int J Mol Sci | Volume | 23 |
| Issue | 21 | PubMed ID | 36362133 |
| Mgi Jnum | J:334183 | Mgi Id | MGI:7385853 |
| Doi | 10.3390/ijms232113340 | Citation | Pape J, et al. (2022) Cardioprotection by Hypothyroidism Is Not Mediated by Favorable Hemodynamics-Role of Canonical Thyroid Hormone Receptor Alpha Signaling. Int J Mol Sci 23(21) |
| abstractText | Hypothyroidism has been shown to reduce infarct size in rats, but the underlying mechanisms are unclear. We used isolated pressure-constant perfused hearts of control, hypothyroid and hyperthyroid mice and measured infarct size, functional parameters and phosphorylation of key molecules in cardioprotective signaling with matched heart rate. Compared with controls, hypothyroidism was cardioprotective, while hyperthyroidism was detrimental with enlarged infarct size. Next, we asked how thyroid hormone receptor alpha (TRalpha) affects ischemia/reperfusion (IR) injury. Thus, canonical and noncanonical TRalpha signaling was investigated in the hearts of (i) mice lacking TRalpha (TRalpha(0)), (ii) with a mutation in TRalpha DNA-binding domain (TRalpha(GS)) and (iii) in hyperthyroid TRalpha(0) (TRalpha(0)hyper) and TRalpha(GS) mice (TRalpha(GS)hyper). TRalpha(0) mouse hearts were protected against IR injury. Furthermore, infarct size was reduced in the hearts of TRalpha(GS) mice that lack canonical TRalpha signaling but maintain noncanonical TRalpha action. Hyperthyroidism did not increase infarct size in TRalpha(0) and TRalpha(GS) mouse hearts. These cardioprotective effects were not associated with increased phosphorylation of key proteins of RISK, SAFE and eNOS pathways. In summary, chronic hypothyroidism and the lack of canonical TRalpha signaling are cardioprotective in IR injury and protection is not due to favorable changes in hemodynamics. |
