GLYCATION ABOLISHES THE CARDIOPROTECTIVE EFFECTS OF ALBUMIN DURING ISCHEMIA-REPERFUSION

Abstract

Although albumin can exert therapeutic effects, diabetes can trigger modifications e.g. advanced glycation end products (AGE) that are associated with cardiovascular complications (1). We therefore hypothesized that albumin glycation results in loss of its cardioprotective properties during ischemia-reperfusion under conditions simulating acute hyperglycemia. Rat hearts were divided into 6 groups: control (11 mM glucose) +/- native bovine serum albumin (BSA) or glycated BSA (BSAgly); and high glucose (33 mM) +/- BSA or BSAgly (n=6 per group). Isolated hearts were subjected to global or regional ischemia protocols as before (2). Immunoblotting was performed on stored ventricular tissues for various markers of the ubiquitin-proteasome system (UPS), oxidative stress, inflammation and apoptosis. These data revealed impaired cardiac function with ischemia-reperfusion under acute hyperglycemic conditions together with enhanced myocardial UPS, AGE and inflammatory markers. This is consistent with our previous findings where higher UPS lowered cardiac function together with increased oxidative stress, inflammation and cell death (3). For the current study, BSA treatment offered cardioprotection by augmenting antioxidant capacity while lowering UPS activation. However, albumin's cardioprotective effects are lost when modified by glycation and BSAgly hearts displayed activated UPS (in part) together with increased inflammation, loss of antioxidant capacity and higher AGE levels.