BACKGROUND AND PURPOSE: Advanced glycation end products (AGEs) and endothelial progenitor cells (EPCs) play key roles in pathogenesis of diabetes-related vascular complications. AGEs can induce dysfunction in EPCs. The peroxisome proliferator-activated receptor-gamma (PPARgamma) agonists are widely used in the treatment of type 2 diabetes, and it remains unknown if they could attenuate EPC dysfunction induced by AGEs. EXPERIMENTAL APPROACH: EPCs isolated from healthy adults were cultured with various concentrations of AGEs (0, 50, 100 and 200 mg L(-1)) with or without rosiglitazone (10 nM), antibody for the receptors for AGE-human serum albumin (anti-receptor for advanced glycation end products (RAGE); 50 microg mL(-1)), phosphatidylinositol-3-kinase (PI3K) inhibitor (LY294002, 5 microM), nitric oxide (NO) synthase inhibitor (L-N(G)-nitro-arginine methyl ester (L-NAME), 100 microM) or sodium nitroprusside (SNP, 25 microM). Proliferation, apoptosis, cell adhesion, migration and NO production in EPCs were assessed, and expressions of endothelial NO synthase (eNOS) and Akt were determined. KEY RESULTS: Number, proliferation/migration capacities, eNOS and Akt phosphorylation as well as NO synthesized by EPCs were increased by rosiglitazone and reduced by AGEs. AGEs promoted while rosiglitazone reduced EPC apoptosis. The AGE-induced effects were significantly ameliorated by pre-incubation with rosiglitazone, RAGE antibody and SNP. The beneficial effects of rosiglitazone could be blocked by pretreatment with L-NAME and LY294002. CONCLUSIONS AND IMPLICATIONS: The PPARgamma agonist rosiglitazone increased EPC function and attenuated EPC dysfunction induced by AGEs via upregulating the Akt-eNOS signal pathways of EPCs.
BACKGROUND AND PURPOSE: Advanced glycation end products (AGEs) and endothelial progenitor cells (EPCs) play key roles in pathogenesis of diabetes-related vascular complications. AGEs can induce dysfunction in EPCs. The peroxisome proliferator-activated receptor-gamma (PPARgamma) agonists are widely used in the treatment of type 2 diabetes, and it remains unknown if they could attenuate EPC dysfunction induced by AGEs. EXPERIMENTAL APPROACH: EPCs isolated from healthy adults were cultured with various concentrations of AGEs (0, 50, 100 and 200 mg L(-1)) with or without rosiglitazone (10 nM), antibody for the receptors for AGE-human serum albumin (anti-receptor for advanced glycation end products (RAGE); 50 microg mL(-1)), phosphatidylinositol-3-kinase (PI3K) inhibitor (LY294002, 5 microM), nitric oxide (NO) synthase inhibitor (L-N(G)-nitro-arginine methyl ester (L-NAME), 100 microM) or sodium nitroprusside (SNP, 25 microM). Proliferation, apoptosis, cell adhesion, migration and NO production in EPCs were assessed, and expressions of endothelial NO synthase (eNOS) and Akt were determined. KEY RESULTS: Number, proliferation/migration capacities, eNOS and Akt phosphorylation as well as NO synthesized by EPCs were increased by rosiglitazone and reduced by AGEs. AGEs promoted while rosiglitazone reduced EPC apoptosis. The AGE-induced effects were significantly ameliorated by pre-incubation with rosiglitazone, RAGE antibody and SNP. The beneficial effects of rosiglitazone could be blocked by pretreatment with L-NAME and LY294002. CONCLUSIONS AND IMPLICATIONS: The PPARgamma agonist rosiglitazone increased EPC function and attenuated EPC dysfunction induced by AGEs via upregulating the Akt-eNOS signal pathways of EPCs.
Authors: B Daan Westenbrink; Erik Lipsic; Peter van der Meer; Pim van der Harst; Hisko Oeseburg; Gideon J Du Marchie Sarvaas; Johan Koster; Adriaan A Voors; Dirk J van Veldhuisen; Wiek H van Gilst; Regien G Schoemaker Journal: Eur Heart J Date: 2007-06-17 Impact factor: 29.983
Authors: Quyen D Chu; Lisa Sun; Jie Li; Kerry Byrnes; Deborah Chervenak; Arrigo DeBenedetti; J Michael Mathis; Benjamin D L Li Journal: J Surg Res Date: 2007-11 Impact factor: 2.192
Authors: Yingmei Feng; Frank Jacobs; Eline Van Craeyveld; Christine Brunaud; Jan Snoeys; Marc Tjwa; Sophie Van Linthout; Bart De Geest Journal: Arterioscler Thromb Vasc Biol Date: 2007-12-06 Impact factor: 8.311
Authors: David A Ingram; Izlin Z Lien; Laura E Mead; Myka Estes; Daniel N Prater; Ethel Derr-Yellin; Linda A DiMeglio; Laura S Haneline Journal: Diabetes Date: 2007-12-17 Impact factor: 9.461
Authors: Andréa E M Stinghen; Ziad A Massy; Helen Vlassara; Gary E Striker; Agnès Boullier Journal: J Am Soc Nephrol Date: 2015-08-26 Impact factor: 10.121
Authors: G Mangialardi; A Monopoli; E Ongini; G Spinetti; O Fortunato; C Emanueli; P Madeddu Journal: Br J Pharmacol Date: 2011-09 Impact factor: 8.739
Authors: Suzanna J Logan; Liya Yin; Werner J Geldenhuys; Molly K Enrick; Kelly M Stevanov; Richard T Carroll; Vahagn A Ohanyan; Christopher L Kolz; William M Chilian Journal: Basic Res Cardiol Date: 2015-03-01 Impact factor: 17.165