Abstract 15664: Angiopoietin-1 Derived From Vascular Smooth Muscle Cells is Essential for Arteriogenesis After Hindlimb Ischemia
Background and Aim: Angiopoietin-1 (Ang1) has been reported to be essential for vascular homeostasis via promoting vascular maturation and integrity. Ang1 conventional knockout (KO) mice show embryonic lethality due to the defects of vascular maturation and heart trabeculation. Vascular smooth muscle cells (VSMCs) constantly secret Ang1 to stabilize vascular endothelial cells through Tie2, a specific receptor for Ang1. However, the role of Ang1 derived from VSMCs in ischemic condition remains unclear to date. Here, we aim to reveal the role of Ang1 derived from VSMCs in angiogenesis and arteriogenesis after ischemia in adulthood.
Methods and Results: We created tamoxifen-induced smooth muscle cell specific Ang1 KO (Ang1SMCKO) mice through crossing floxed Ang1 (Ang1flox/flox) mice with SM-MHC-Cre(ER)T2 mice. We subjected control and Ang1SMCKO mice to a hindlimb ischemia (HLI). Ang1SMCKO mice showed significantly impaired blood flow recovery and treadmill-running capacity compared with control on and after 10 days in response to HLI. Whereas the capillary angiogenesis evaluated by anti-CD31-immunostaining was almost comparable between control and Ang1SMCKO mice, arteriogenesis and collateral formation evaluated by both anti-alpha-SMA immunostaining and X-ray microangiography were significantly impaired in Ang1SMCKO mice compared with those in control. Furthermore, Ang1SMCKO mice displayed enhanced vascular permeability after HLI compared with control. Additionally, we created transgenic mice overexpressing potent Ang1 analogue COMP-Ang1 in smooth muscle cells (SM-Ang1-TG mice) through crossing CAGp-IND-COMP-Ang1 Tg mice with SM-MHC-Cre(ER)T2 mice. Intriguingly, SM-Ang1-TG mice exhibited systemically enhanced blood flow in both skins and skeletal muscles with enlarged arterioles and capillary vessels evaluated by CD31-immunostaining.
Conclusion: Ang1 derived from VSMCs plays a critical role in arteriogenesis and collateral formation after HLI.
Author Disclosures: K. Ikeoka: None. Y. Nakaoka: None. Y. Arita: None. T. Hashimoto: None. T. Yasui: None. T. Masaki: None. K. Yamauchi-Takihara: None. M. Shirai: None. I. Komuro: None. Y. Sakata: None.
- © 2014 by American Heart Association, Inc.