Kalofutis, Christos (2012) The impact of diabetes on cardiac remodelling after myocardial infarction: potential role of thyroid hormone signalling. Doctoral thesis, University of Central Lancashire.
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Diabetes (DM) increases mortality after myocardial infarction and deteriorates post-ischaemic cardiac remodelling. This study investigated possible implications of thyroid hormone (TH) signalling in either reducing or preventing this response. TH signalling has a regulatory role in metabolism, cardiac function, growth and ischaemic stress. Acute myocardial infarction (AMI) was induced in age–match healthy control rats (AMI-C) and in streptozotocin (STZ)-induced type I diabetic (DM) animals (DM+AMI) using 35 mg/kg body weight while sham operated animals served as controls (SHAM). The results show that AMI in tissue hypothyroidism caused significant down-regulation of TH receptors, TRα1 and TRβ1, in the diabetic myocardium without changes in T3, T4 levels in plasma. This response was associated with increased expression of β-MHC and distinct changes in cardiac function and geometry. Ejection fractions (EF%) was decreased in DM-AMI as compared to DM+AMI animals. Systolic and diastolic chamber dimensions were increased without concomitant increase in wall thickness and thus, WTI (the ratio of LVIDd/2*Posterior Wall thickness), an index of wall stress, was significantly elevated. The absence of wall thickening in DM+AMI hearts was associated with changes in stretch-induced kinase hypertrophic signalling p38 MAPK. In contrast, ERK, p-ERK and p-p38 MAPK levels were not changed in DM+AMI as compared to non-infarcted hearts (DM+SHAM). TH administration after AMI prevented hypothyroidism and resulted in decreased β-MHC expression, increased wall thickening and normalized wall stress, while stretch-induced p38 MAPK activation was restored. The results show that diabetes can exacerbates post-ischaemic cardiac remodelling and tissue hypothyroidism and TH treatment can prevent this response and improve cardiac haemodynamics.
|Item Type:||Thesis (Doctoral)|
|Additional Information:||Mol. Cell. Biochem (2010) 345:161-169|
|Uncontrolled Keywords (separate with ;):||Cardiac Remodelling ; TH signalling ; myocardial infarction|
|Schools:||Faculty of Clinical & Biomedical Sciences > School of Pharmacy and Biomedical Sciences|
|Deposited By:||Hayley Gayle Moran|
|Deposited On:||10 Jan 2013 16:15|
|Last Modified:||10 Feb 2017 12:42|
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