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Cytokines / Chemokines in Angiogenesis Proteins

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Cytokines / Chemokines in Angiogenesis Proteins

Cytokines / Chemokines in Angiogenesis Proteins Background

Cytokines

The cytokines that affect angiogenesis are mainly vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF).

Basic fibroblast growth factor (bFGF)

FGF2 (Figure 1), also known as basic fibroblast growth factor (bFGF) and FGF-β, is a growth factor and signaling protein encoded by the FGF2 gene. It is mainly synthesized as a 155 amino acid polypeptide, producing 18 kDa protein. Like other FGF family members, basic fibroblast growth factor has extensive mitogenic and cell viability activities and is involved in a variety of biological processes including embryonic development, cell growth, morphogenesis, tissue repair, tumor growth and invasion. In normal tissues, bFGF is present in the subendothelial extracellular matrix of the basement membrane and blood vessels. As long as there is no signal peptide, it remains in a membrane-bound state. It is speculated that in the healing of normal tissues and the development of tumors, the action of heparan sulfate-degrading enzymes activates bFGF, which mediates the formation of new blood vessels, a process called angiogenesis.

Figure 1. Structure of the FGF2 protein.

Vascular endothelial growth factor (VEGF)

Vascular endothelial growth factor (VEGF), originally known as vascular permeability factor (VPF), is a signaling protein that stimulates angiogenesis in cells. In particular, VEGF is a subfamily of growth factors and is a family of growth factors of the platelet-derived cystine growth factor family. They are important signaling proteins involved in angiogenesis (former formation of the embryonic circulatory system) and angiogenesis (vascular growth from existing blood vessels). It is part of the system and can restore the oxygen supply to the tissue when blood circulation is insufficient (for example, under hypoxic conditions). The concentration of VEGF in serum of patients with bronchial asthma and diabetes is higher. The normal function of VEGF is to create new blood vessels during embryonic development. After injury, the muscles after exercise produce new blood vessels and bypass new blood vessels that block blood vessels (collateral circulation). When VEGF is overexpressed, it may cause disease. Without adequate blood supply, solid cancer cannot develop to a limited scale. Cancers that express VEGF are capable of growth and metastasis. Overexpression of VEGF can cause retinal vascular disease in the eye and other parts of the body. Drugs such as aflibercept, bevacizumab, ranibizumab and pegaptanib can inhibit VEGF and control or slow down these diseases.

Figure 2. Structure of protein VEGFC.

Chemokines

Chemokines can affect angiogenesis, or promote angiogenesis by proliferating endothelial cells, causing vascular endothelial cell proliferation, capillary formation, or inhibiting angiogenesis by inhibiting the activity of various pro-angiogenic factors. Chemokines and a variety of other angiogenesis-related factors form a network that participates in the regulation of angiogenesis. In addition, the CXC family chemokine SDF-1α is also involved in the development of gastrointestinal vasculature. Studies have shown that CXC chemokines in chemokines have a direct effect on angiogenesis. Among the CC family chemokines, MCP-1 can directly promote angiogenesis, and I-309 and eotaxin can also promote angiogenesis.

CXC chemokines

The structural feature of CXC chemokines is that the two N-terminal Cys residues are separated by one amino acid residue, which is mainly produced by activated monocytes, endothelial cells, fibroblasts and megakaryocytes. Most members can chemotaxis and activate neutrophils. T cells and B cells can also be chemotactic. The CXC chemokine receptor is a complete membrane protein that specifically binds to and responds to cytokines of the CXC chemokine family. They represent a subfamily of chemokine receptors, a large family of G-protein-linked receptors known as seven transmembrane (7-TM) proteins because they span the cell membrane seven times. There are currently seven known CXC chemokine receptors in mammals, designated CXCR1 to CXCR7.

Figure 3. Structure of CXC chemokine receptor 4.

MCP-1

Chemokine (C-C motif) ligand 2 (CCL2), also known as monocyte chemoattractant protein 1 (MCP1) and small inducible cytokine A2, is a small cytokine belonging to the CC chemokine family. CCL2 recruit monocytes, memory T cells and dendritic cells to sites of inflammation resulting from tissue damage or infection.

Figure 4. Structure of monocyte chemoattractant protein 1 (MCP1).

References:

1. Tsai HH.; et al. The chemokine receptor CXCR2 controls positioning of oligodendrocyte precursors in developing spinal cord by arresting their migration. Cell. 2002.110 (3): 373–83.

2. Xu, Y. F.; et al. A new expression plasmid in Bifidobacterium longum as a delivery system of endostatin for cancer gene therapy. Cancer gene therapy. 2007, 14(2), 151-157.

3. Carr MW.; et al. Monocyte chemoattractant protein 1 acts as a T-lymphocyte chemoattractant. Proceedings of the National Academy of Sciences of the United States of America. 1994, 91 (9): 3652–6.

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