Angiopoietin

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(Redirected from
Angiopoietin-2
)
Not to be confused with angiogenin.
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Angiopoietin is part of a family of vascular

smooth muscle cells surrounding vessels.[3]
There are now four identified angiopoietins:
ANGPT1, ANGPT2, ANGPTL3, ANGPT4.[4]

In addition, there are a number of proteins that are closely related to ('like') angiopoietins (Angiopoietin-related protein 1, ANGPTL2, ANGPTL3, ANGPTL4, ANGPTL5, ANGPTL6, ANGPTL7, ANGPTL8).[5]

Angiopoietin-1 is critical for vessel maturation, adhesion, migration, and survival. Angiopoietin-2, on the other hand, promotes cell death and disrupts vascularization. Yet, when it is in conjunction with vascular endothelial growth factors, or

VEGF, it can promote neo-vascularization.[6]

Structure

C-terminal fibrinogen-related domain responsible for the binding between the ligand and receptor.[6]

Angiopoietin-1 encodes a 498 amino acid

polypeptide with a molecular weight of 57 kDa whereas angiopoietin-2 encodes a 496 amino acid polypeptide.[7]

Only clusters/multimers activate receptors

Angiopoietin-1 and angiopoietin-2 can form dimers, trimers, and tetramers. Angiopoietin-1 has the ability to form higher order multimers through its super clustering domain. However, not all of the structures can interact with the tyrosine kinase receptor. The receptor can only be activated at the tetramer level or higher.[6]

Specific mechanisms

Tie pathway

The collective interactions between angiopoietins,

enzymes
, a process known as cell signaling.

Tie-2

Tie-2/Ang-1 signaling activates β1-

osteoblastic cells.[8]
Although which specific TIE receptors mediate signals downstream of angiogenesis stimulation is highly contested, it is clear that TIE-2 is capable of activation as a result of binding angiopoietins.

Angiopoietin proteins 1 through 4 are all

macrophages for immune responses.[6] Angiopoietin-1 is a growth factor produced by vascular support cells, specialized pericytes in the kidney, and hepatic stellate cells (ITO) cells in the liver. This growth factor is also a glycoprotein and functions as an agonist for the tyrosine receptor found in endothelial cells.[9] Angiopoietin-1 and tyrosine kinase signaling are essential for regulating blood vessel development and the stability of mature vessels.[9]

The expression of Angiopoietin-2 in the absence of vascular endothelial growth factor (VEGF) leads to endothelial cell death and vascular regression.[10] Increased levels of Ang2 promote tumor angiogenesis, metastasis, and inflammation. Effective means to control Ang2 in inflammation and cancer should have clinical value.[11] Angiopoeitin, more specifically Ang-1 and Ang-2, work hand in hand with VEGF to mediate angiogenesis. Ang-2 works as an antagonist of Ang-1 and promotes vessel regression if VEGF is not present. Ang-2 works with VEGF to facilitate cell proliferation and migration of endothelial cells.[12] Changes in expression of Ang-1, Ang-2 and VEGF have been reported in the rat brain after cerebral ischemia.[13][14]

Angiogenesis signaling

To migrate, the endothelial cells need to loosen the endothelial connections by breaking down the

chemokines play an essential role. VEGF and ang-1 are involved in endothelial tube formation.[15]

Vascular permeability signaling

Angiopoietin-1 and angiopoietin-2 are modulators of endothelial permeability and barrier function. Endothelial cells secrete angiopoietin-2 for

parenchymal cells of the extravascular tissue secrete angiopoietin-2 onto endothelial cells for paracrine signaling, which then binds to the extracellular matrix and is stored within the endothelial cells.[7]

Cancer

Angiopoietin-2 has been proposed as a biomarker in different cancer types. Angiopoietin-2 expression levels are proportional to the cancer stage for both small and non-small cell lung cancers. It has been also implicated to play role in hepatocellular and endometrial carcinoma-induced angiogenesis. Experiments using blocking antibodies for angiopoietin-2 have shown to decrease metastasis to lungs and lymph nodes.[16]

Clinical relevance

Deregulation of angiopoietin and the tyrosine kinase pathway is common in blood-related diseases such as diabetes, malaria,[17] sepsis, and pulmonary hypertension. This[clarification needed] is demonstrated by an increased ratio of angiopoietin-2 and angiopoietin-1 in blood serum. To be specific, angiopoietin levels provide an indication for sepsis. Research on angiopoietin-2 has shown that it is involved in the onset of septic shock. The combination of fever and high levels of angiopoietin-2 are correlated with a greater prospect of the development of septic shock. It has also been shown that imbalances between angiopoietin-1 and angiopoietin-2 signaling can act independently of each other. One angiopoietin factor can signal at high levels while the other angiopoieting factor remains at baseline level signaling.[2]

Angiopoietin-2 is produced and stored in

Weibel-Palade bodies in endothelial cells and acts as a TEK tyrosine kinase antagonist. As a result, the promotion of endothelial activation, destabilization, and inflammation are promoted. Its role during angiogenesis depends on the presence of Vegf-a.[9]

Serum levels of angiopoietin-2 expression are associated with the growth of

squamous cell carcinoma.[19] Circulating angiopoietin-2 is a marker for early cardiovascular disease in children on chronic dialysis.[20] Kaposi's sarcoma-associated herpesvirus induces rapid release of angiopoietin-2 from endothelial cells.[21]

Angiopoietin-2 is elevated in patients with angiosarcoma.[22]

Research has shown angiopoietin signaling to be relevant in treating cancer as well. During tumor growth, pro-angiogenic molecules and anti-angiogenic molecules are off balance. Equilibrium is disrupted such that the number of pro-angiogenic molecules are increased. Angiopoietins have been known to be recruited as well as VEGFs and platelet-derived growth factors (

PDGFs). This is relevant for clinical use relative to cancer treatments because the inhibition of angiogenesis can aid in suppressing tumor proliferation.[23]

References

  1. PMID 15893672
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  2. ^
    PMID 20509945
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  3. ISBN 978-0-87893-558-1
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  4. PMID 10051567
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  5. PMID 24478758
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  6. ^
    PMID 22922303
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  7. ^
    ISBN 978-1-61504-120-6
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  8. PMID 20614597
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  9. ^
    PMID 21606590
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  10. ISBN 0-306-47988-5
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  11. PMID 23500414
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  12. PMID 15562207
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  13. PMID 21334414
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  14. PMID 24412374
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  15. ^ Félétou, M. (2011). "Chapter 2, Multiple Functions of the Endothelial Cells.". The Endothelium: Part 1: Multiple Functions of the Endothelial Cells—Focus on Endothelium-Derived Vasoactive Mediators. San Rafael, CA: Morgan & Claypool Life Sciences.
  16. PMID 31108880
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  17. PMID 32565839
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  18. S2CID 12275550
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  19. S2CID 41226861
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  20. PMID 23409162
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  21. PMID 23536671
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  22. S2CID 7399513
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  23. PMID 19815705
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External links
Retrieved from "https://en.wikipedia.org/w/index.php?title=Angiopoietin&oldid=1213901100"