Laminar shear stress stimulates vascular smooth muscle cell apoptosis via the Akt pathway. Export

@article{citeulike:2998369, abstract = {Vascular smooth muscle cells (SMC) may be directly exposed to blood flow after an endothelial-denuding injury. It is not known whether direct exposure of SMC to shear stress reduces SMC turnover and contributes to the low rate of restenosis after most vascular interventions. This study examines if laminar shear stress inhibits SMC proliferation or stimulates apoptosis. Bovine aortic SMC were exposed to arterial magnitudes of laminar shear stress (11 dynes/cm(2)) for up to 24 h and compared to control SMC (0 dynes/cm(2)). SMC density was assessed by cell counting, DNA synthesis by (3)[H]-thymidine incorporation, and apoptosis by TUNEL staining. Akt, caspase, bax, and bcl-2 phosphorylation were assessed by Western blotting; caspase activity was also measured with an in vitro assay. Analysis of variance was used to compare groups. SMC exposed to laminar shear stress had a 38\% decrease in cell number (n = 4, P = 0.03), 54\% reduction in (3)[H]-thymidine incorporation (n = 3, P = 0.003), and 15-fold increase in TUNEL staining (n = 4, P < 0.0001). Akt phosphorylation was reduced by 67\% (n = 3, P < 0.0001), whereas bax/bcl-2 phosphorylation was increased by 1.8-fold (n = 3, P = 0.01). Caspase-3 activity was increased threefold (n = 5, P = 0.03). Pretreatment of cells with ZVAD-fmk or wortmannin resulted in 42\% increased cell retention (n = 3, P < 0.01) and a fourfold increase in apoptosis (n = 3, P < 0.04), respectively. Cells transduced with constitutively-active Akt had twofold decreased apoptosis (n = 3, P < 0.002). SMC exposed to laminar shear stress have decreased proliferation and increased apoptosis, mediated by the Akt pathway. These results suggest that augmentation of SMC apoptosis may be an alternative strategy to inhibit restenosis after vascular injury.}, address = {Department of Surgery, Yale University School of Medicine, New Haven, Connecticut 06519, USA.}, author = {Fitzgerald, T. N. and Shepherd, B. R. and Asada, H. and Teso, D. and Muto, A. and Fancher, T. and Pimiento, J. M. and Maloney, S. P. and Dardik, A.}, citeulike-article-id = {2998369}, citeulike-linkout-0 = {http://dx.doi.org/10.1002/jcp.21404}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/18247368}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=18247368}, doi = {10.1002/jcp.21404}, issn = {1097-4652}, journal = {Journal of cellular physiology}, keywords = {akt, apoptosis, shear, smc}, month = {August}, number = {2}, pages = {389--395}, posted-at = {2008-07-14 08:53:56}, priority = {3}, title = {Laminar shear stress stimulates vascular smooth muscle cell apoptosis via the Akt pathway.}, url = {http://dx.doi.org/10.1002/jcp.21404}, volume = {216}, year = {2008} }

TY - JOUR ID - citeulike:2998369 L3 - citeulike-article-id:2998369 N2 - Vascular smooth muscle cells (SMC) may be directly exposed to blood flow after an endothelial-denuding injury. It is not known whether direct exposure of SMC to shear stress reduces SMC turnover and contributes to the low rate of restenosis after most vascular interventions. This study examines if laminar shear stress inhibits SMC proliferation or stimulates apoptosis. Bovine aortic SMC were exposed to arterial magnitudes of laminar shear stress (11 dynes/cm(2)) for up to 24 h and compared to control SMC (0 dynes/cm(2)). SMC density was assessed by cell counting, DNA synthesis by (3)[H]-thymidine incorporation, and apoptosis by TUNEL staining. Akt, caspase, bax, and bcl-2 phosphorylation were assessed by Western blotting; caspase activity was also measured with an in vitro assay. Analysis of variance was used to compare groups. SMC exposed to laminar shear stress had a 38% decrease in cell number (n = 4, P = 0.03), 54% reduction in (3)[H]-thymidine incorporation (n = 3, P = 0.003), and 15-fold increase in TUNEL staining (n = 4, P < 0.0001). Akt phosphorylation was reduced by 67% (n = 3, P < 0.0001), whereas bax/bcl-2 phosphorylation was increased by 1.8-fold (n = 3, P = 0.01). Caspase-3 activity was increased threefold (n = 5, P = 0.03). Pretreatment of cells with ZVAD-fmk or wortmannin resulted in 42% increased cell retention (n = 3, P < 0.01) and a fourfold increase in apoptosis (n = 3, P < 0.04), respectively. Cells transduced with constitutively-active Akt had twofold decreased apoptosis (n = 3, P < 0.002). SMC exposed to laminar shear stress have decreased proliferation and increased apoptosis, mediated by the Akt pathway. These results suggest that augmentation of SMC apoptosis may be an alternative strategy to inhibit restenosis after vascular injury. IS - 2 JF - Journal of cellular physiology SN - 1097-4652 AD - Department of Surgery, Yale University School of Medicine, New Haven, Connecticut 06519, USA. EP - 395 TI - Laminar shear stress stimulates vascular smooth muscle cell apoptosis via the Akt pathway. VL - 216 SP - 389 KW - akt KW - apoptosis KW - shear KW - smc AU - Fitzgerald, TN AU - Shepherd, BR AU - Asada, H AU - Teso, D AU - Muto, A AU - Fancher, T AU - Pimiento, JM AU - Maloney, SP AU - Dardik, A PY - 2008/08// UR - http://dx.doi.org/10.1002/jcp.21404 ER -