Abstract
The formation of new blood vessels from pre-existing vasculature, the process known as angiogenesis, is highly regulated by pro- and anti-angiogenic signaling molecules including growth factors and proteases. As an endothelial cell-surface co-receptor for plasminogen and tissue plasminogen activator, the annexin A2 (ANXA2) complex accelerates plasmin generation and facilitates fibrinolysis. Plasmin can subsequently activate a downstream proteolytic cascade involving multiple matrix metalloproteinases. Thus, in addition to maintaining blood vessel patency, the ANXA2 complex can also promote angiogenesis via its pro-fibrinolytic activity. The generation of ANXA2-deficient mice allowed us to first observe the pro-angiogenic role of ANXA2 in vivo. Further investigations have provided additional details regarding the mechanism for ANXA2 regulation of retinal and corneal angiogenesis. Other studies have reported that ANXA2 supports angiogenesis in specific tumor-related settings. Here, we summarize results from in vivo studies that illustrate the pro-angiogenic role of ANXA2, and discuss the critical questions that may lead to an advanced understanding of the molecular mechanisms for ANXA2-mediated angiogenesis. Finally, highlights from studies on ANXA2-interacting agents offer potential therapeutic opportunities for the application of ANXA2-centered pharmaceuticals in angiogenesis-related disorders.
Acknowledgments
This work was supported by grants to KAH from the National Heart, Lung, and Blood Institute (HL042493), the U.S. Department of Defense (MR130194), the March of Dimes Foundation 6-FY15-356, and the Qatar National Research Fund (5-932-3-208 and 6-736-3-187).
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©2016 Walter de Gruyter GmbH, Berlin/Boston
Articles in the same Issue
- Frontmatter
- Guest Editorial
- Highlight: annexins in health and disease
- HIGHLIGHT: ANNEXINS IN HEALTH AND DISEASE
- Emerging functions as host cell factors – an encyclopedia of annexin-pathogen interactions
- Annexins in plasma membrane repair
- Annexin A1: shifting the balance towards resolution and repair
- Annexin A1 and resolution of inflammation: tissue repairing properties and signalling signature
- Annexins A2 and A8 in endothelial cell exocytosis and the control of vascular homeostasis
- The annexin A2 system and angiogenesis
- More than just innate affairs – on the role of annexins in adaptive immunity
- Annexins – insights from knockout mice
- Review
- Regulation of Rap GTPases in mammalian neurons
- Research Articles/Short Communications
- Protein Structure and Function
- Insights into K-Ras 4B regulation by post-translational lysine acetylation
- Cell Biology and Signaling
- MicroRNA-544 down-regulates both Bcl6 and Stat3 to inhibit tumor growth of human triple negative breast cancer
Articles in the same Issue
- Frontmatter
- Guest Editorial
- Highlight: annexins in health and disease
- HIGHLIGHT: ANNEXINS IN HEALTH AND DISEASE
- Emerging functions as host cell factors – an encyclopedia of annexin-pathogen interactions
- Annexins in plasma membrane repair
- Annexin A1: shifting the balance towards resolution and repair
- Annexin A1 and resolution of inflammation: tissue repairing properties and signalling signature
- Annexins A2 and A8 in endothelial cell exocytosis and the control of vascular homeostasis
- The annexin A2 system and angiogenesis
- More than just innate affairs – on the role of annexins in adaptive immunity
- Annexins – insights from knockout mice
- Review
- Regulation of Rap GTPases in mammalian neurons
- Research Articles/Short Communications
- Protein Structure and Function
- Insights into K-Ras 4B regulation by post-translational lysine acetylation
- Cell Biology and Signaling
- MicroRNA-544 down-regulates both Bcl6 and Stat3 to inhibit tumor growth of human triple negative breast cancer