Abstract 14683: Endoglin and ALK1 Act Differently of Ischemia and Shear Stress Induced Neovascularization
Introduction: TGF- β stimulates both ischemia induced angiogenesis and shear stress induced arteriogenesis, by signaling through different receptors. In this study the role of TGF-β receptors ALK1 and endoglin is assessed in a model for hind limb ischemia induced neovascularization in mice.
Methods and Results: Femoral artery ligation was performed in mice heterozygous for either endoglin, or ALK1 and in littermate controls. Blood flow recovery, monitored by laser doppler perfusion imaging, was significantly hampered in both endoglin and ALK1 heterozygous mice compared to controls by maximal 40% and 49%, respectively. Collateral artery size was significantly reduced in endoglin heterozygous mice compared to controls, but not in ALK1 heterozygous mice. Capillary density in ischemic calf muscles was unaffected, but capillaries from endoglin and ALK1 heterozygous mice were significantly larger when compared to controls. To provide mechanistic evidence for the differential role of endoglin and ALK1 in shear induced or hypoxia induced neovascularization, murine endothelial cells were exposed to shear stress in vitro. This induced high levels of endoglin messengerRNA, but not ALK1.
Conclusion: Here we demonstrated that both endoglin and ALK1 play a crucial role in blood flow recovery. Importantly, endoglin is essential in both shear induced collateral artery growth and in ischemia induced angiogenesis, whereas ALK1 is only involved in ischemia induced angiogenesis.
- © 2011 by American Heart Association, Inc.