Abstract 533: Shear-Induced Collateral Artery Growth Modulated by Endoglin but Not by ALK1
Introduction: TGF- β stimulates both shear stress induced arteriogenesis and ischemia induced angiogenesis, by signaling through different receptors. In this study the role of TGF-β receptors ALK1 and endoglin is assessed in a murine model for hind limb ischemia induced neovascularization.
Methods and Results: Femoral artery ligation was performed in mice heterozygous for either endoglin, or ALK1 and 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. Furthermore, both endoglin and ALK1 heterozygous mice showed significant more erythrocyte extravasation near the capillaries than their littermate controls, pointing towards less mature capillaries. Murine endothelial cells were exposed to shear stress in vitro to study the differential role of endoglin and ALK1 in shear induced neovascularization. This resulted in high levels of endoglin messengerRNA, but not of 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.
- © 2012 by American Heart Association, Inc.