Gerald Proteau

Peripheral blood lymphocytes from patients with bipolar disorder demonstrate apoptosis and differential regulation of advanced glycation end products and S100B

Abstract Background: This study addresses the expression of the glycosylated proteins known as advanced glycation end products (AGEs), the calcium binding protein S100B and the apoptotic parameters cytochome c and caspase-3 activity in peripheral lymphocyte cytosolic extracts from a sample of bipolar disorder (BD) patients and healthy (control) subjects. Methods: Cross-sectional study of 35 patients with a clinical diagnosis of bipolar disease (10 euthymic, 12 depressed, 13 manic) and 10 healthy control subjects. Lymphocytes were used as a surrogate model in BD diagnosis and treatment. AGEs and S100B in lymphocyte cell extracts were measured by commercially available enzyme-linked immunosorbent assay. Results: AGEs were lower in all BD patients compared to healthy subjects. Depressed patients had approximately two-fold higher S100B levels compared to healthy subjects. Manic and depressed BD patients had increased superoxide dismutase mRNA levels. Apoptosis as measured by BAX/Bcl2 ratio, cytochrome c release, caspase-3 activity was increased in manic and depressed patients compared to healthy subjects. In the depressed patients, S100B levels correlated with cytochrome c release. Conclusions: In conclusion, our study shows decreased AGEs and increased S100B levels and caspase down-stream apoptosis in peripheral lymphocytes of BD patients that may underlie disease etiopathogenesis.

S100B: Role in cardiac remodeling and function following myocardial infarction in diabetes

AIM S100B plays a role in cardiac remodeling following myocardial infarction (MI) and in diabetic vascular complications but not examined in diabetic myocardium. We thus examined the effects of targeted deletion of S100B gene on post-MI hearts. MAIN METHODS Coronary artery ligation or sham was performed 15 weeks after streptozotocin (STZ) or vehicle injection in wild-type (WT) and S100B knock-out (BKO) mice. Left ventricular (LV) structural and functional remodeling was studied 35 days after induction of MI. KEY FINDINGS In diabetes, post-MI remodeling exhibited an attenuated increase in LV mass, dilation, and myocyte hypertrophy in association with increased apoptosis and fibrosis and reduced matrix metalloproteinase-2 (MMP-2) activity. Despite reduced LV dilation, impairment of cardiac function was similar to non-diabetic controls. Both diabetes and MI alone induced myocardial S100B and its canonical receptor for advanced glycation end product (RAGE) expression. By contrast, in post-MI diabetic myocardium, S100B expression was attenuated. Diabetic BKO, following MI demonstrated increased ventricular dilation compared to WT, in association with greater impairment of cardiac function, GLUT4 expression and systemic AGE levels. SIGNIFICANCE These data suggest that S100B expression may serve to modulate cardiac metabolism and adverse consequences of AGE in diabetic post-MI remodeling and function.

Increased myocardial expression of angiopoietin-2 in patients undergoing urgent surgical revascularization for acute coronary syndromes

BACKGROUND Myocardial ischemia triggers the expression of multiple angiogenic factors including vascular endothelial growth factor and its receptors. However, vascular endothelial growth factor does not act in isolation. OBJECTIVE To identify other genes important in the angiogenic response to clinically relevant myocardial ischemia. METHODS AND RESULTS Paired intraoperative biopsies of ischemic and nonischemic myocardium were obtained from 12 patients with acute coronary syndromes (ACS) undergoing urgent coronary artery bypass graft surgery. Real-time polymerase chain reaction demonstrated significant upregulation of angiopoietin-2 (Ang-2) in ischemic myocardium, to a greater extent than other classical angiogenic factors. Microarray gene profiling identified Ang-2 to be among the top 10 differentially upregulated genes, in addition to genes involved in inflammation, cell signalling, remodelling and apoptosis. CONCLUSIONS The present document is the first report of microarray analysis of patients with ACS, and supports an important role for Ang-2 in the angiogenic response to severe ischemia in the human heart. Common gene expression patterns in ACS may provide opportunities for targeted pharmacological and cellular intervention.