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October 14, 2014
1:00 PM - 3:00 PM
Room Room 275-277
Oxidative Stress Leads to Altered Gene Expression in Cardiac Myocytes Following Cardiopulmonary Bypass in Patients with Poorly Controlled Type II Diabetes vs. Non-Diabetics
Jeffrey Hubbard, M.D., M.S., Thomas Huang, B.A., Khurram Owais, M.D., Vwaire Orhurhu, B.A., M.P.H., Anam Pal, M.D., Mario Montealegre, M.D., Kamal Khabbaz, M.D., Feroze Mahmood, M.D., Robina Matyal, M.D.
Beth Israel Deaconess, Boston, Massachusetts, United States
Oxidative Stress Leads To Altered Gene Expression in Cardiac Myocytes following Cardiopulmonary Bypass in Patients with Poorly Controlled Type II Diabetes vs. Non-Diabetics


Diabetes Mellitus type II causes functional and molecular changes, which consequently leads to severe cardiomyopathy, neuropathy, and worse clinical outcomes following cardiopulmonary bypass. The signaling cascade associated with these clinical findings has yet to be completely understood. We hypothesize that variation of the mitogen associated protein kinase (MAPK) pathway signaling plays a role in mediating the changes seen in uncontrolled diabetic patients vs. non-diabetics leading to adverse effects.


Right atrial appendage tissue from 40 patients was collected pre- and post-cardiopulmonary bypass (CPB) and functional data was assessed. Patients were divided into two groups based on a clinical diagnosis of diabetes and an HbA1c count greater than or equal to 6.5. There were 20 non-diabetic (ND) patients and 20 diabetic (D) patients. The gene expression was subsequently measured using microarray analysis.


Gene expression profiles compared 1207 genes that varied between diabetic and non-diabetic patients. Microarray data revealed significantly altered gene expression in several interrelated factors that have been shown to be associated with inflammatory responses and oxidative stress. We found several genes of specific interest that have a role in regulating the MAPK pathway. MAPK14 and MKNK1 were both shown to be down regulated by 1.44 fold (p=0.035) and 1.80 fold (p=0.024) in D patients in comparison to ND respectively. Where as, MAPKAPK3 and IL6R were determined to be up regulated in D patients versus ND patients. MAPKAPK3 had a 1.12 fold increase (p=0.043), and IL6R increased 1.18 fold (p= 0.040)


Our findings suggest that there is correlation between the MAPK pathway and the genes expressed in right atrial appendage cardiac myocytes when they undergo CPB resulting in damage that leads to adverse conditions seen post operatively in patients with a HbgA1c above 6.5.
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