9-LB: Effects of Hyperglycemia-Induced Stress in a Human Cardiomyocyte Cell Line

Abstract

The prevalence of diabetes in America has continued to increase over the past years, affecting 10.5% of the US population. Cardiomyopathy is one of the major complications of long-term diabetes. Diabetic cardiomyopathy is characterized by an increase in the thickness and rigidity of the heart wall resulting in contractile dysfunction that can ultimately result in heart failure. Hyperglycemia has been also associated with an increase in the production of reactive oxygen species and inflammatory mediators. In the current study, we investigated the role of hyperglycemic exposure to cardiomyocyte in altering the epigenetic markers such as histone deacetylases (HDACs) and inflammatory mediators (such as TLR4 and RAGE) in the progression of cardiomyocyte remodeling and hypertrophy. Cardiac damage was assessed by analyzing the expression of cardiac structural proteins such as Troponin I&T and Connexin43 (Cx43). AC16 cardiomyocyte cell line derived from adult ventricular heart tissue was subjected to high glucose conditions (25 mM) for 24 hours and stress mediated markers were assessed by Western Blot and immunocytochemistry. The statistical significance of the difference between groups was determined by ANOVA (systat 13 software, SPSS Inc., Chicago, IL, USA), using Bonferroni correction for the multiple post hoc analyses for each control and hyperglycemic conditions. An increase in class I HDAC expression (HDAC2) was observed, with no changes seen in the expression of class II HDACs (HDAC 4 and 6). A downregulation of CXCR4 was observed, suggestive of its role as a cardioprotective agent. Increased levels of oxidative stress markers such as RAGE and TLR4 were seen, along with increased expression of markers of cardiac injury such as Cx43 and Troponin I&T. These findings suggest that epigenetic mechanisms and oxidative stress-mediated inflammatory markers can alter the functionality of cardiomyocytes exposed to high glucose conditions. Disclosure H. Waghela: None. V. Thakur: None. M. Chattopadhyay: None. Funding Texas Tech University Health Sciences Center El Paso (183381SEED)