Caveolin-1 expression is critical for vascular endothelial growth factor-induced ischemic hindlimb collateralization and nitric oxide-mediated angiogenesis. Export

@article{citeulike:844783, abstract = {Nitric oxide (NO) is a powerful angiogenic mediator acting downstream of vascular endothelial growth factor (VEGF). Both the endothelial NO synthase (eNOS) and the VEGFR-2 receptor colocalize in caveolae. Because the structural protein of these signaling platforms, caveolin, also represses eNOS activity, changes in its abundance are likely to influence the angiogenic process in various ways. In this study, we used mice deficient for the caveolin-1 gene (Cav-/-) to examine the impact of caveolae suppression in a model of adaptive angiogenesis obtained after femoral artery resection. Evaluation of the ischemic tissue perfusion and histochemical analyses revealed that contrary to Cav+/+ mice, Cav-/- mice failed to recover a functional vasculature and actually lost part of the ligated limbs, thereby recapitulating the effects of the NOS inhibitor L-NAME administered to operated Cav+/+ mice. We also isolated endothelial cells (ECs) from Cav-/- aorta and showed that on VEGF stimulation, NO production and endothelial tube formation were dramatically abrogated when compared with Cav+/+ ECs. The Ser1177 eNOS phosphorylation and Thr495 dephosphorylation but also the ERK phosphorylation were similarly altered in VEGF-treated Cav-/- ECs. Interestingly, caveolin transfection in Cav-/- ECs redirected the VEGFR-2 in caveolar membranes and restored the VEGF-induced ERK and eNOS activation. However, when high levels of recombinant caveolin were reached, VEGF exposure failed to activate ERK and eNOS. These results emphasize the critical role of caveolae in ensuring the coupling between VEGFR-2 stimulation and downstream mediators of angiogenesis. This study also provides new insights to understand the paradoxical roles of caveolin (eg, repressing basal enzyme activity but facilitating activation on agonist stimulation) in cardiovascular pathophysiology.}, address = {University of Louvain Medical School, Unit of Pharmacology and Therapeutics, Brussels, Belgium.}, author = {Sonveaux, P. and Martinive, P. and DeWever, J. and Batova, Z. and Daneau, G. and Pelat, M. and Ghisdal, P. and Gr\'{e}goire, V. and Dessy, C. and Balligand, J. L. and Feron, O.}, citeulike-article-id = {844783}, citeulike-linkout-0 = {http://dx.doi.org/10.1161/01.RES.0000136344.27825.72}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/15205364}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=15205364}, day = {23}, doi = {10.1161/01.RES.0000136344.27825.72}, issn = {1524-4571}, journal = {Circ Res}, keywords = {balance, caveolin-1, enos, erk12, vegfr2}, month = {July}, number = {2}, pages = {154--161}, posted-at = {2006-09-15 11:34:55}, priority = {0}, title = {Caveolin-1 expression is critical for vascular endothelial growth factor-induced ischemic hindlimb collateralization and nitric oxide-mediated angiogenesis.}, url = {http://dx.doi.org/10.1161/01.RES.0000136344.27825.72}, volume = {95}, year = {2004} }

TY - JOUR ID - citeulike:844783 L3 - citeulike-article-id:844783 N2 - Nitric oxide (NO) is a powerful angiogenic mediator acting downstream of vascular endothelial growth factor (VEGF). Both the endothelial NO synthase (eNOS) and the VEGFR-2 receptor colocalize in caveolae. Because the structural protein of these signaling platforms, caveolin, also represses eNOS activity, changes in its abundance are likely to influence the angiogenic process in various ways. In this study, we used mice deficient for the caveolin-1 gene (Cav-/-) to examine the impact of caveolae suppression in a model of adaptive angiogenesis obtained after femoral artery resection. Evaluation of the ischemic tissue perfusion and histochemical analyses revealed that contrary to Cav+/+ mice, Cav-/- mice failed to recover a functional vasculature and actually lost part of the ligated limbs, thereby recapitulating the effects of the NOS inhibitor L-NAME administered to operated Cav+/+ mice. We also isolated endothelial cells (ECs) from Cav-/- aorta and showed that on VEGF stimulation, NO production and endothelial tube formation were dramatically abrogated when compared with Cav+/+ ECs. The Ser1177 eNOS phosphorylation and Thr495 dephosphorylation but also the ERK phosphorylation were similarly altered in VEGF-treated Cav-/- ECs. Interestingly, caveolin transfection in Cav-/- ECs redirected the VEGFR-2 in caveolar membranes and restored the VEGF-induced ERK and eNOS activation. However, when high levels of recombinant caveolin were reached, VEGF exposure failed to activate ERK and eNOS. These results emphasize the critical role of caveolae in ensuring the coupling between VEGFR-2 stimulation and downstream mediators of angiogenesis. This study also provides new insights to understand the paradoxical roles of caveolin (eg, repressing basal enzyme activity but facilitating activation on agonist stimulation) in cardiovascular pathophysiology. IS - 2 JF - Circ Res SN - 1524-4571 AD - University of Louvain Medical School, Unit of Pharmacology and Therapeutics, Brussels, Belgium. EP - 161 TI - Caveolin-1 expression is critical for vascular endothelial growth factor-induced ischemic hindlimb collateralization and nitric oxide-mediated angiogenesis. VL - 95 SP - 154 KW - balance KW - caveolin-1 KW - enos KW - erk12 KW - vegfr2 AU - Sonveaux, P AU - Martinive, P AU - DeWever, J AU - Batova, Z AU - Daneau, G AU - Pelat, M AU - Ghisdal, P AU - Grégoire, V AU - Dessy, C AU - Balligand, JL AU - Feron, O PY - 2004/07/23/ UR - http://dx.doi.org/10.1161/01.RES.0000136344.27825.72 ER -