Τίτλος:
Dose-dependent effects of thyroid hormone on post-ischemic cardiac performance: Potential involvement of Akt and ERK signalings
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
The present study explored the effects of thyroid hormone (TH) treatment on post-ischemic cardiac function and potential implicated mechanisms. Acute myocardial infarction (AMI) was induced in mice by coronary artery ligation while sham-operated animals served as controls. This procedure resulted in a marked depression of cardiac function and significant reduction in TH levels in plasma. TH was given at a dose aiming to normalize T3 levels in plasma [AMI-TH (A)] and also at higher doses. The group of animals treated with the highest dose of TH, which displayed significantly increased mortality rate was included in the study [AMI-TH (B)]. In AMI-TH (A) mice, TH significantly improved left ventricular (LV) ejection fraction (EF%), [27.9% (1.4) in AMI versus 38.0 (3.1) in AMI-TH (A), P < 0.05], and favorably remodeled LV chamber while α-MHC was the dominant isoform expressed. In AMI-TH (B) mice, TH treatment resulted in increased mortality as compared to untreated mice (73% vs 47%, P < 0.05), while the favorable effect of TH was not evident in the survived animals. At the molecular level, TH, at the replacement dose, modestly increased p-Akt levels in the myocardium without any change in p-ERK levels. On the contrary, TH at the higher dose resulted in further increase in p-Akt along with an increase in p-ERK levels. In conclusion, TH appears to have a dose-dependent bimodal effect on post-ischemic cardiac performance and this effect may, at least in part, be mediated by a distinct pattern of activation of Akt and ERK signaling. © 2011 Springer Science+Business Media, LLC.
Συγγραφείς:
Mourouzis, I.
Mantzouratou, P.
Galanopoulos, G.
Kostakou, E.
Roukounakis, N.
Kokkinos, A.D.
Cokkinos, D.V.
Pantos, C.
Περιοδικό:
Molecular and Cellular Biochemistry
Λέξεις-κλειδιά:
liothyronine; mitogen activated protein kinase; myosin heavy chain alpha; protein kinase B; thyroid hormone; thyroxine, acute heart infarction; animal experiment; animal model; article; concentration response; congestive heart failure; controlled study; heart function; heart left ventricle contractility; heart left ventricle ejection fraction; heart muscle; heart muscle injury; heart muscle tension; heart performance; heart rate; heart ventricle hypertrophy; heart ventricle remodeling; liothyronine blood level; male; mortality; mouse; nonhuman; post ischemic cardiac function; protein expression; protein phosphorylation; thyroid hormone blood level; thyroxine blood level, Animals; Disease Models, Animal; Dose-Response Relationship, Drug; Extracellular Signal-Regulated MAP Kinases; Heart Rate; Hormone Replacement Therapy; Male; Mice; Mice, Inbred C57BL; Myocardial Contraction; Myocardial Infarction; Myocardium; Myosin Heavy Chains; Phosphorylation; Proto-Oncogene Proteins c-akt; Signal Transduction; Stroke Volume; Thyroxine; Triiodothyronine; Ventricular Function, Left; Ventricular Remodeling, Animalia; Mus
DOI:
10.1007/s11010-011-1175-9
