title: 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.
abstract: CONCLUSIONS
  Heart failure (HF) is a dominant cause for the higher mortality of diabetics after myocardial infarction (MI). In the present investigation, we have discovered that higher levels of oxidative stress (OS)-induced carbonylated proteins accompany worsening post-MI HF in the presence of type 1 diabetes. These findings provide a mechanistic link between amplified OS and exacerbation of post-infarction HF in diabetes.
  
  
  BACKGROUND
  Type 1 diabetes mellitus (DM) patients surviving myocardial infarction (MI) manifest an increased incidence of subsequent heart failure (HF). 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 surviving LV myocardium of MI and DM+MI rats in relation to residual LV function.
  
  
  METHODS
  Type 1 DM was induced in rats via administration of streptozotocin. Two weeks after induction of type 1 DM, MI was produced in DM and non-DM rats by coronary artery ligation. Residual LV function and remodeling was assessed at 4 weeks post-MI by echocardiography. Myocardial carbonylated proteins were detected through OxyBlot analysis, and identified by mass spectrometry.
  
  
  RESULTS
  Compared with MI rats, DM+MI rats exhibited significantly poorer residual LV systolic function and elevated wet to dry weight ratios of the lungs. Protein carbonyl content in cardiac tissue and isolated heart mitochondria of DM+MI rats was 20% and 48% higher, respectively, versus MI rats. Anti-oxidative enzymes and fatty acid utilization proteins were among the carbonylated protein candidates identified.
  
  
  CONCLUSIONS
  These findings implicate myocardial protein carbonylation as part of the molecular pathophysiology of aggravated HF in the type 1 diabetic post-infarction heart.
authors.affiliation: Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
authors.forename: Kathleen E
authors.initials: KE
authors.lastname: Dennis
authors.forename: Salisha
authors.initials: S
authors.lastname: Hill
authors.forename: Kristie L
authors.initials: KL
authors.lastname: Rose
authors.forename: Uchechukwu K A
authors.initials: UK
authors.lastname: Sampson
authors.forename: Michael F
authors.initials: MF
authors.lastname: Hill
mesh_terms: D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology; D003922:Diabetes Mellitus, Type 1 / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology; D004798:Enzymes / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism; D006333:Heart Failure / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D008929:Mitochondria, Heart / Q000378:metabolism; D009203:Myocardial Infarction / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism*; D018384:Oxidative Stress; D050050:Protein Carbonylation; D051381:Rats; D012720:Severity of Illness Index; D013599:Systole; D016277:Ventricular Function, Left; D020257:Ventricular Remodeling
chemical_list: D004798:Enzymes; D005227:Fatty Acids
keywords: Carbonylation; Heart failure; Myocardial infarction; Oxidative stress; Type 1 diabetes mellitus