Impaired Collateral Vessel Development Associated With Reduced Expression of Vascular Endothelial Growth Factor in ApoE −/− Mice

• DOI: 10.1161/01.cir.99.24.3188
• Publication Date: 2012-06-12T00:42:29Z
• Authors: Thierry Couffinhal; Marcy Silver; Marianne Kearney; Alison Sullivan; Bernhard Witzenbi...; Meredith Magner; Brian Annex; Kevin Peters; Jeffrey M. Isner
• Keywords: Arteriogenesis; Hindlimb; Apolipoprotein E; Immunostaining; Collateral circulation

Background —The impact of disordered lipid metabolism on collateral vessel development was studied in apolipoprotein (apo)E −/− mice with unilateral hindlimb ischemia. Methods and Results —Hindlimb blood flow capillary density were markedly reduced apoE versus C57 controls. This associated expression vascular endothelial growth factor (VEGF) the ischemic limbs mice. Cell-specific immunostaining localized VEGF protein to skeletal myocytes infiltrating T cells mice; contrast, T-cell infiltrates severely reduced. The critical contribution reinforced by finding accelerated limb necrosis athymic nude operatively induced Adenoviral gene transfer resulted marked augmentation density. Conclusions —These findings thus underscore extent which hyperlipidemia adversely affects native but does not preclude augmented response exogenous cytokines. Moreover, results obtained imply a role for as source neovascularization tissues.