Intramyocardial protein therapy with vascular endothelial growth factor (VEGF-165) induces functional angiogenesis in rat senescent myocardium. - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Journal of Physiology and Pharmacology Année : 2010

Intramyocardial protein therapy with vascular endothelial growth factor (VEGF-165) induces functional angiogenesis in rat senescent myocardium.

Résumé

Myocardial capillary density and angiogenesis are impaired during aging but whether growth factor therapy is able to induce functional neovascularization in senescent heart have never been studied. In 3, 24, 28 and 32 mo male Wistar rats, cardiac hemodynamic measurements indicated heart failure at 28 and 32 mo, associated with left ventricular hypertrophy. VEGF/VEGF-R2, Ang-1/Ang-2/Tie-2 and PTN levels, quantitated in left ventricle by western blotting and immunohistochemistry, showed that VEGF and VEGF-R2 levels were specifically decreased during aging. In vitro angiogenesis ± rhVEGF-165 (5 and 50 ng/mL) was measured in aortic segments in 3D-collagen. Aortic sprouting was decreased during aging but restored by VEGF treatment (P<0.001), similarly in 3 and 24 mo with 50 ng/mLVEGF. Finally, 3 and 24 mo rats were submitted to in vivo intramyocardial rhVEGF-165 (10 micrograms) or saline solution injection and angiogenesis was measured by SPECT imaging of the alpha(v)beta(3) integrin-targeted tracer (99m)Tc-RAFT-RGD, capillary fluorescence staining in isolated perfused heart and vWF and alpha smooth muscle actin immunohistochemistry, 7 and 21 days later. VEGF administration increased capillary density in 3 but also in 24 mo rats at days 7 (+26%, P<0.01) and 21 (+41%, P<0.01) and arteriolar density at day 21 (+36%, P<0.01). Activity of (99m)Tc-RAFT-RGD and capillary fluorescence labeling indicated that new formed capillaries were functional. Cardiac aging was associated with strong VEGF/VEGF-R2 pathway downregulation. VEGF-165 protein therapy was able to induce in vitro and in vivo angiogenesis during aging. In 24 mo hearts, in vivo angiogenesis was functional, sustained and comparable to neovascularization observed in 3 mo hearts.
Fichier principal
Vignette du fichier
2010_JPP_SB_.pdf (1.51 Mo) Télécharger le fichier
Origine : Fichiers éditeurs autorisés sur une archive ouverte
Loading...

Dates et versions

hal-00688199 , version 1 (17-04-2012)

Identifiants

  • HAL Id : hal-00688199 , version 1
  • PUBMED : 21224495

Citer

Sophie Besse, François Boucher, Gilberte Linguet, Laurent Riou, Joël de Leiris, et al.. Intramyocardial protein therapy with vascular endothelial growth factor (VEGF-165) induces functional angiogenesis in rat senescent myocardium.. Journal of Physiology and Pharmacology, 2010, 61 (6), pp.651-61. ⟨hal-00688199⟩
1837 Consultations
192 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More