Thyroid hormone can favorably remodel the diabetic myocardium after acute myocardial infarction

Abstract

It has been previously shown that regulators of physiological growth such as thyroid hormone (TH) can favorably remodel the post ischaemic myocardium. Here, we further explored whether this effect can be preserved in the presence of co-morbidities such as diabetes which accelerates cardiac remodeling and increases mortality after myocardial infarction. Acute myocardial infarction (AMI) was induced by left coronary ligation in rats with type I diabetes (DM) induced by streptozotocin administration (STZ; 35 mg/kg; i.p.) while sham-operated animals served as controls (SHAM). AMI resulted in distinct changes in cardiac function and geometry; EF% was significantly decreased in DM-AMI [37.9 ± 2.0 vs. 74.5 ± 2.1 in DM-SHAM]. Systolic and diastolic chamber dimensions were increased without concomitant increase in wall thickness and thus, wall tension index [WTI, the ratio of (Left Ventricular Internal Diameter at diastole)/2*(Posterior Wall thickness)], an index of wall stress, was found to be significantly increased in DM-AMI; 2.27 ± 0.08 versus 1.70 ± 0.05. 2D-Strain echocardiographic analysis showed reduced systolic radial strain in all segments, indicating increased loss of cardiac myocytes in the infarct related area and less compensatory hypertrophy in the viable segments. This response was accompanied by a marked decrease in the expression of TRα1 and TRβ1 receptors in the diabetic myocardium without changes in circulating T3 and T4. Accordingly, the expression of TH target genes related to cardiac contractility was altered; β-MHC and PKCα were significantly increased. TH (L-T4 and L-T3) administration prevented these changes and resulted in increased EF%, normal wall stress and increased systolic radial strain in all myocardial segments. Acute myocardial infarction in diabetic rats results in TH receptor down-regulation with important physiological consequences. TH treatment prevents this response and improves cardiac hemodynamics.

The Emerging Role of TRα1 in Cardiac Repair: Potential Therapeutic Implications

“…The reparative effect of TH seems to be mediated via activation of prosurvival signaling pathways. Thus, TH activates Akt [16, 59–61] and regulates PKC isoforms expression [62, 63], HSP70 expression [64], and HSP27 expression and phosphorylation and translocation [65]. Furthermore, TH suppresses ischemia/reperfusion induced p38 MAPK and JNK activation [14, 66].…”

Thyroid hormone and recovery of cardiac function in patients with acute myocardial infarction: a strong association?

“…Furthermore, changes in TH in plasma are linked to high mortality both in patients with heart failure (5) and those with AMI (8), indicating potential implication of TH signaling in the post-ischemic cardiac recovery. Interestingly, this hypothesis has recently been addressed in experimental models of ischemia-reperfusion and myocardial infarction in animals and accumulating evidence reveals that TH is critical for the response of the myocardium to ischemic stress and TH may possess cytoprotective properties that are 'silent' in healthy tissue, manifesting only during stress (10)(11)(12)(13).…”

Thyroid Hormone and Cardiac Disease: From Basic Concepts to Clinical Application

“…Several lines of experimental evidence support this notion [24–29] (Figure 3). Thus, TH treatment early after infarction resulted in marked improvement of contractile indices independent of loading conditions, such as +dp/dt and −dp/dt, due to favorable cell remodeling as indicated by the switch of MHC isoform expression from the fetal to adult pattern [26].…”