Tags

Type your tag names separated by a space and hit enter

Caveolin-1 expression is critical for vascular endothelial growth factor-induced ischemic hindlimb collateralization and nitric oxide-mediated angiogenesis.
Circ Res. 2004 Jul 23; 95(2):154-61.CircR

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.

Authors+Show Affiliations

University of Louvain Medical School, Unit of Pharmacology and Therapeutics, Brussels, Belgium.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15205364

Citation

Sonveaux, Pierre, et al. "Caveolin-1 Expression Is Critical for Vascular Endothelial Growth Factor-induced Ischemic Hindlimb Collateralization and Nitric Oxide-mediated Angiogenesis." Circulation Research, vol. 95, no. 2, 2004, pp. 154-61.
Sonveaux P, Martinive P, DeWever J, et al. Caveolin-1 expression is critical for vascular endothelial growth factor-induced ischemic hindlimb collateralization and nitric oxide-mediated angiogenesis. Circ Res. 2004;95(2):154-61.
Sonveaux, P., Martinive, P., DeWever, J., Batova, Z., Daneau, G., Pelat, M., Ghisdal, P., Grégoire, V., Dessy, C., Balligand, J. L., & Feron, O. (2004). Caveolin-1 expression is critical for vascular endothelial growth factor-induced ischemic hindlimb collateralization and nitric oxide-mediated angiogenesis. Circulation Research, 95(2), 154-61.
Sonveaux P, et al. Caveolin-1 Expression Is Critical for Vascular Endothelial Growth Factor-induced Ischemic Hindlimb Collateralization and Nitric Oxide-mediated Angiogenesis. Circ Res. 2004 Jul 23;95(2):154-61. PubMed PMID: 15205364.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Caveolin-1 expression is critical for vascular endothelial growth factor-induced ischemic hindlimb collateralization and nitric oxide-mediated angiogenesis. AU - Sonveaux,Pierre, AU - Martinive,Philippe, AU - DeWever,Julie, AU - Batova,Zuzana, AU - Daneau,Géraldine, AU - Pelat,Michel, AU - Ghisdal,Philippe, AU - Grégoire,Vincent, AU - Dessy,Chantal, AU - Balligand,Jean-Luc, AU - Feron,Olivier, Y1 - 2004/06/17/ PY - 2004/6/19/pubmed PY - 2005/2/9/medline PY - 2004/6/19/entrez SP - 154 EP - 61 JF - Circulation research JO - Circ Res VL - 95 IS - 2 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. SN - 1524-4571 UR - https://www.unboundmedicine.com/medline/citation/15205364/Caveolin_1_expression_is_critical_for_vascular_endothelial_growth_factor_induced_ischemic_hindlimb_collateralization_and_nitric_oxide_mediated_angiogenesis_ DB - PRIME DP - Unbound Medicine ER -