084 Diabetes prevents compensatory hypertrophy after myocardial infarction and impairs cardiac function; possible implication of stretch induced kinase growth signaling

Aim The present study investigated possible mechanisms underlying postischemic remodeling in diabetic hearts. Diabetes (DM) accelerates postischaemic cardiac remodeling and increases mortality after myocardial infarction. Methods Acute myocardial infarction (AMI) was induced in rats with type I diabetes (DM) and non diabetic rats (NDM-AMI) while sham operated animals served as controls (SHAM). All groups were subjected to echocardiographic analysis 2 weeks after infarction. Results AMI resulted in increased expression of β-MHC and distinct changes in cardiac function and geometry. EF% was decreased in DM-AMI as compared to NDM-AMI. 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 increased in DM-AMI hearts. The absence of wall thickening in DM-AMI hearts was associated with different pattern of activation of stretch induced kinase hypertrophic signaling p38 MAPK and ERK; Phosphorylated ERK and p38 MAPK levels were increased in NDM-AMI hearts, while were not changed in DM-AMI as compared to non infarcted diabetic hearts (DM-SHAM). TH administration after AMI resulted in decreased β-MHC expression, increased wall thickening and normalized wall stress, while stretch induced p38 MAPK activation was restored. Conclusions Diabetes reduces the ability of the myocardium to adapt after myocardial infarction by preventing the development of compensatory hypertrophy. This is, at least in part due to inactivation of stress induced kinase signalling.