Related Experiment Video
Updated: Oct 7, 2025
07:52
Implantation of Fibrin Gel on Mouse Lung to Study Lung-specific Angiogenesis
Published on: December 21, 2014
10.2K
The Plasminogen-Activator Plasmin System in Physiological and Pathophysiological Angiogenesis
Asmaa Anwar Ismail1,2, Baraah Tariq Shaker1,2, Khalid Bajou1,2
1Department of Applied Biology, College of Sciences, University of Sharjah, Sharjah 27272, United Arab Emirates.
International Journal of Molecular Sciences
|January 11, 2022
Summary
The plasminogen activator-plasmin system regulates angiogenesis, a process crucial for new blood vessel formation. Targeting this system, particularly plasminogen activators and their inhibitors, offers therapeutic strategies for cancer and other neovascularization-related diseases.
Area of Science:
- Biochemistry
- Molecular Biology
- Cell Biology
Background:
- Angiogenesis, the formation of new blood vessels from pre-existing ones, is vital in physiological and pathological contexts.
- The plasminogen activator-plasmin system is a key regulator of extracellular matrix remodeling, essential for endothelial cell migration and proliferation during angiogenesis.
- This system involves urokinase/tissue-type plasminogen activators (uPA/tPA) and their inhibitor PAI-1, influencing proteolysis and cell signaling.
Purpose of the Study:
- To elucidate the multifaceted roles of the plasminogen activator-plasmin system in angiogenesis.
- To explore the paradoxical pro-angiogenic functions of plasminogen activator inhibitor-1 (PAI-1).
- To investigate the contribution of urokinase-type plasminogen activator receptor (uPAR) to endothelial cell migration in angiogenesis.
Main Methods:
- Analysis of the molecular mechanisms governing the plasminogen activator-plasmin system in angiogenesis.
- Examination of PAI-1 expression and function in endothelial cells during angiogenesis.
- Investigation of uPAR-mediated signaling pathways involved in endothelial cell migration.
Main Results:
- uPA/tPA activate plasminogen to plasmin, which degrades the extracellular matrix and releases pro-angiogenic factors like VEGF-A.
- PAI-1, despite inhibiting uPA/tPA, paradoxically promotes angiogenesis by modulating plasmin-mediated proteolysis and enhancing cell migration via vitronectin.
- uPAR contributes to endothelial cell migration during angiogenesis through interactions with specific signaling partners.
Conclusions:
- The plasminogen activator-plasmin system is a critical regulator of angiogenesis, with complex roles for its components.
- Targeting serine proteases within this system, or their interactions, presents a promising therapeutic avenue for controlling pathological neovascularization, including tumor growth.
- Further understanding of these molecular interactions is essential for developing effective anti-angiogenic therapies.
Keywords:
angiogenesisendothelial cellsplasminplasminogen-activator inhibitor-1 (PAI-1)urokinase-plasminogen activator (uPA)vascular endothelial growth factor (VEGF)More Related Videos
Related Concept Videos
01:16Clot Retraction and Fibrinolysis
7.3K
After a fibrin clot is formed, the next step is clot retraction, a vital process facilitated by platelet contractile proteins, such as actin and myosin. These proteins pull the fibrin strands closer together and condense the clot. This action reduces the size of the clot, creating a smaller, denser structure that effectively seals off the damaged vessel. Clot retraction consolidates the clot and helps with wound healing by bringing the edges of the damaged blood vessel closer together.
7.3K
01:10Mechanism of Angiogenesis
6.0K
Blood vessel formation starts early during embryonic development, around day 7. In the extraembryonic yolk sac, mesodermal precursor cells called hemangioblast proliferate and differentiate into angioblast. Angioblasts express vascular endothelial growth factor receptor 2 or VEGFR2, which binds VEGF-A, a proangiogenic factor, guiding blood vessel formation. VEGF signaling promotes angioblasts to form a blood island in the developing embryo. Angioblasts further differentiate, giving rise to...
6.0K
01:24Regulation of Angiogenesis and Blood Supply
2.8K
Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits. Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
2.8K
01:22Formation of the Platelet Plug
7.6K
The platelet phase, the second stage of hemostasis, commences around 15-20 seconds after an injury. It follows and overlaps with the vascular phase, during which blood vessels constrict to minimize blood loss.
As the injured blood vessel contracts, endothelial cells undergo contraction, revealing collagen fibers in the basement membrane and underlying connective tissue. Furthermore, the plasma membrane of endothelial cells becomes adhesive, preparing the site for platelet adhesion. Platelets...
As the injured blood vessel contracts, endothelial cells undergo contraction, revealing collagen fibers in the basement membrane and underlying connective tissue. Furthermore, the plasma membrane of endothelial cells becomes adhesive, preparing the site for platelet adhesion. Platelets...
7.6K
01:30Anticoagulant Drugs: Low-Molecular-Weight Heparins
1.0K
Hemostasis is a crucial process that prevents excessive blood loss from damaged blood vessels. It involves various mechanisms such as vasoconstriction, platelet adhesion and activation, and fibrin formation. The importance of each mechanism depends on the type of vessel injury. In contrast, thrombosis is the abnormal formation of a blood clot within the blood vessels, leading to potential complications if the clot obstructs blood flow. Thrombosis can be caused by increased coagulability of the...
1.0K
01:20Extrinsic and Intrinsic Pathways of Hemostasis
9.9K
Blood clotting or coagulation involves extrinsic and intrinsic pathways, which ultimately merge into the common pathway, forming a fibrin clot.
The Extrinsic Pathway
The extrinsic pathway of coagulation is typically initiated by tissue damage that exposes blood to tissue factor (TF), a protein released by the damaged tissue cells outside the blood vessels—this interaction with TF triggers biochemical reactions involving specific clotting factors. The key player here is Factor VII, which...
The Extrinsic Pathway
The extrinsic pathway of coagulation is typically initiated by tissue damage that exposes blood to tissue factor (TF), a protein released by the damaged tissue cells outside the blood vessels—this interaction with TF triggers biochemical reactions involving specific clotting factors. The key player here is Factor VII, which...
9.9K