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Insufficient HO1 Response to Ischemic Stress Correlates with Increased Inflammation and Reduced Survival of EPCs in Diabetic Patients
Author(s) -
Issan Yossi,
Hochhauser Edith,
Kornowski Ran,
Leshem-Lev Dorit,
Lev Eli,
Sharoni Ram,
Vanella Luca,
Puri Nitin,
Laniado-Schwartzman Michal,
Abraham Nader G,
Porat Eyal
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.1114.11
Subject(s) - tbars , adiponectin , oxidative stress , medicine , inflammation , diabetes mellitus , endocrinology , proinflammatory cytokine , heme oxygenase , antioxidant , thiobarbituric acid , insulin resistance , heme , lipid peroxidation , chemistry , biochemistry , enzyme
Background Diabetes is characterized by oxidative stress and systemic inflammation. Nuclear ‐E2‐related factor‐2 (Nrf2) is a transcription factor that activate of various antioxidant genes, including heme oxygenase‐1 (HO‐1). HO‐1 and adiponectin are cardioprotective ensuing ischemia reperfusion Methods adipose tissue from diabetic (n=15) and non‐diabetic (n=15) patients undergoing CABG was analyzed using RT‐PCR and immunoblotting for Nrf2 genes. Oxidative stress was evaluated by thiobarbituric acid‐reactive substance (TBARS). Peripheral blood, was evaluated for inflammatory cytokines and EPC markers. Results Compared to controls, TBARS were higher in diabetic patients. Although Nrf2‐dependent antioxidant proteins (TxR1, NQO1, GST) were upregulated, HO‐1 and adiponectin protein expression and serum levels of bilirubin were lower in diabetic patients. Inflammatory cytokines serum levels were higher in diabetic patients. EPC levels and function were significantly reduced with diminished viability in diabetic group. Conclusion These results demonstrate for the first time that there is an inadequate HO‐1‐adiponectin axis response in humans with chronic conditions of oxidative stress such as diabetic patients with severe coronary artery disease, leading to insufficient antioxidant and anti‐inflammatory outcome.