Effet de la concentration du glucose circulant sur la fonction vasculaire au cours du vieillissement. Action sur les flux calciques et la vasomotricité induite par les peptides d’élastine

Excess apoptosis of endothelial cells (EC) plays crucial roles in the onset and progression of vasculopathy in diabetes mellitus. Anion exchanger-2 (AE2) might be involved in the vasculopathy. However, little is known about the molecular mechanisms that AE2 mediated the apoptosis of EC. The purpose of this study was to explore the role of AE2 in the apoptosis of HUVECs induced by high glucose (HG) and its possible mechanisms. First, HUVECs were exposed to different glucose concentrations (5.5, 17.8, 35.6, 71.2 and 142.4 mmol/l, respectively, pH = 7.40) for different time points (12, 24, 48, 72, 120, and 168 h, respectively). Intracellular Cl(-) concentration ([Cl(-)]i), AE2 expression and the apoptosis were assayed. Then, 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS), Cl(-)-free media or specific RNA interference (RNAi) for AE2 was used to confirm whether AE2 could mediate the apoptosis induced by HG. Finally, the mechanisms of the AE2-mediated apoptosis were investigated by detecting mitochondrial permeability transition pore (mPTP, DeltaPsim) openings, reactive oxygen species (ROS) levels and Caspase-3 activity. We found that HG upregulated the AE2 expression and activity, increased [Cl(-)]i and induced the apoptosis in a time- and concentration-dependent manner. The apoptosis of HUVECs by HG was possibly mediated by AE2 through an mPTP-ROS-Caspase-3 dependent pathway. These findings suggested that AE2 was likely to be a glucose-sensitive transmembrane transporter and a novel potential therapeutic target for diabetic vasculopathy.

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Involvement of anion exchanger-2 in apoptosis of endothelial cells induced by high glucose through an mPTP-ROS-Caspase-3 dependent pathway

Huang

Chen

et al. 2010

Apoptosis

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Binding of elastin peptides to S‐Gal protects the heart against ischemia/reperfusion injury by triggering the RISK pathway

et al. 2007

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Elastin peptides (EPs) generated by hydrolysis of elastic fibers by elastinolytic enzymes display a wide spectrum of biological activities. Here, we investigated their influence on rat heart ischemia-mediated injury using the Langendorff ex vivo model. EPs, i.e., kappa elastin, at 1.32- and 660-nM concentrations, when administered before the ischemia period, elicited a beneficial influence against ischemia by accelerating the recovery rate of heart contractile parameters and by decreasing significantly creatine kinase release and heart necrosis area when measured at the onset of the reperfusion. All effects were S-Gal-dependent, as being reproduced by (VGVAPG)3 and as being inhibited by receptor antagonists, such as lactose and V14 peptide (VVGSPSAQDEASPL). EPs interaction with S-Gal triggered NO release and activation of PI3-kinase/Akt and ERK1/2 in human coronary endothelial cells (HCAECs) and rat neonatal cardiomyocytes (RCs). This signaling pathway, as designated as RISK, for reperfusion injury salvage kinase pathway, was shown to be responsible for the beneficial influence of EPs on ischemia/reperfusion injury on the basis of its inhibition by specific pharmacological inhibitors. EPs survival activity was attained at a concentration averaging that present into the blood circulation, supporting the contention that these matrikines might offer a natural protection against cardiac injury in young and adult individuals. Such protective effect might be lost with aging, since we found that hearts from 24-month-old rats did not respond to EPs.

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Effet de la concentration du glucose circulant sur la fonction vasculaire au cours du vieillissement. Action sur les flux calciques et la vasomotricité induite par les peptides d’élastine

Abstract: Effet de la concentration du glucose circulant sur la fonction vasculaire au cours du vieillissement. Action sur les flux calciques et la vasomotricité induite par les peptides d'élastine

Cited by 2 publications

References 50 publications

Involvement of anion exchanger-2 in apoptosis of endothelial cells induced by high glucose through an mPTP-ROS-Caspase-3 dependent pathway

Involvement of anion exchanger-2 in apoptosis of endothelial cells induced by high glucose through an mPTP-ROS-Caspase-3 dependent pathway

Binding of elastin peptides to S‐Gal protects the heart against ischemia/reperfusion injury by triggering the RISK pathway

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