Abstract 9111: Augmented Cardiac Formation of Oxidatively-Induced Carbonylated Proteins Accompanies the Increased Functional Severity of Post-Myocardial Infarction Heart Failure in the Setting of Type 1 Diabetes Mellitus
Type 1 diabetes mellitus (DM) patients surviving myocardial infarction (MI) have substantially higher cardiovascular mortality than those without DM. We have previously shown that after MI, type 1 DM is associated with accentuated myocardial oxidative stress (OS) and concomitant worsening of left ventricular (LV) function. However, the precise mechanisms whereby type 1 DM-enhanced OS adversely affects HF after MI remain obscure. As carbonylation of proteins is an irreversible post-translational modification induced only by OS that often leads to the loss of function, we analyzed protein-bound carbonyls in the viable LV myocardium of MI and DM + MI rats in relation to residual LV function at 4 weeks post-MI. Type 1 DM was induced in male Sprague-Dawley rats by a single injection of streptozotocin (65 mg/kg i.p.). Two weeks after induction of type 1 DM, MI was produced in DM and non-DM rats by left coronary artery ligation. Residual LV function was assessed by echocardiography. Carbonylated proteins were detected through oxyblot analysis, and identified by mass spectrometry. Mortality following induction of MI was higher among the DM + MI group compared to the MI group (47% vs. 33%, respectively). Compared with MI rats, DM + MI rats exhibited significantly greater LV systolic dysfunction as well as elevated wet to dry weight ratios of the lungs (Table), indicating an increased functional severity of HF among the DM + MI group. No difference in the weight of myocardial scar caused by the infarction was observed between the MI and DM + MI groups (Table). Protein carbonyl content in cardiac tissue and isolated mitochondria of DM + MI rats was 20% and 48% higher, respectively, than in MI rats (n=4/group). Anti-oxidative enzymes and fatty acid utilization proteins were the predominant carbonylated proteins identified. The findings of this in vivo study implicate protein carbonylation as part of the molecular pathophysiology of aggravated HF in the type 1 diabetic post-infarction heart.
- © 2012 by American Heart Association, Inc.