title: [Type 1 diabetes impairs compensatory response after myocardial infarction; role of tissue hypothyroidism and effects of thyroid hormone administration].
abstract: Type 1 diabetes (TOD) increases the risk of coronary artery disease and myocardial infarction and is characterized by baseline cardiac dysfunction. We investigated the influence of TOD in post-infarct remodeling (REM) and the role of thyroid hormone (TH) signaling in this response. Acute myocardial infarction (AMI) was induced in rats with type I diabetes (TOD) and in non diabetic rats (NTOD-AMI), sham-operated rats serving as controls (SHAM). AMI resulted in tissue hypothyroidism due to significant downregulation of the TH receptors TRa1 and TRbeta1 in the TOD myocardium, while no change in plasma T3 or T4 was observed This response was associated with increased expression of beta-MHC and distinct changes in cardiac function and geometry: EF % was decreased in TOD-AMI as compared to NTOD-AMI. Systolic and diastolic chamber dimensions were increased, with no concomitant increase in wall thickness. Thus, WTI (the ratio of LVIDd/2 x posterior wall thickness), an index of wall stress, was significantly increased in TOD-AMI. The absence of wall thickening in TOD-AMI hearts was associated with changes in stretch-induced kinase hypertrophic signaling: phosporylated (p) ERK and p-p38 MAPK levels were not changed in TOD-AMI in comparison with non infarcted hearts (TOD-SHAM) and NTOD-A MI hearts. TH administration after AMI prevented tissue hypothyroidism and resulted in decreased beta-MHC expression, increased wall thickening and normalized wallstress, while stretch-induced p38 MAPK activation was increased. We conclude that diabetes exacerbates post-ischemic cardiac remodeling and that tissue hypothyroidism may be involved in this response.
authors: Département Cardiovasculaire, Fondation de Recherches Iatrobiologiques de l'Académie d'Athènes, 4 Soranou Ephessiou Str, 115 27 Athens, Greece. dcokkinos@bioacademy.gr
authors: Dennis V
authors: DV
authors: Cokkinos
authors: Constantinos
authors: C
authors: Pantos
mesh_terms: D000818:Animals; D003922:Diabetes Mellitus, Type 1 / Q000503:physiopathology*; D007037:Hypothyroidism / Q000378:metabolism*; D008297:Male; D009203:Myocardial Infarction / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D013974:Thyroxine / Q000008:administration & dosage; D014284:Triiodothyronine / Q000008:administration & dosage; D020257:Ventricular Remodeling / Q000502:physiology*
chemical_list: D014284:Triiodothyronine; D013974:Thyroxine