Target type: biologicalprocess
The directed movement of an endothelial cell guided by a specific chemical concentration gradient. Movement may be towards a higher concentration (positive chemotaxis) or towards a lower concentration (negative chemotaxis). [CL:0000115, GOC:BHF]
Endothelial cell chemotaxis is a crucial process in angiogenesis, the formation of new blood vessels. It involves the directed migration of endothelial cells towards a chemoattractant gradient, a concentration gradient of a chemical signal. Here's a detailed breakdown of the biological process:
1. **Chemoattractant Production:** Various factors can stimulate the production of chemoattractants, including:
* **Hypoxia:** Low oxygen levels in tissues trigger the release of factors like vascular endothelial growth factor (VEGF) and angiopoietin-1.
* **Inflammation:** Inflammatory mediators like TNF-α and IL-1β can also induce the production of chemoattractants.
* **Wound Healing:** Growth factors like PDGF and TGF-β are released during wound healing, attracting endothelial cells to the injured site.
2. **Chemoattractant Reception:** Endothelial cells possess specific receptors on their surface that bind to chemoattractants. These receptors are typically G protein-coupled receptors (GPCRs), such as VEGFR2, which binds to VEGF.
3. **Signal Transduction:** Upon binding to the receptor, the chemoattractant activates a signaling cascade within the endothelial cell. This cascade involves various intracellular messengers, such as:
* **Phosphoinositide 3-kinase (PI3K):** Activates downstream signaling pathways involved in cell survival and migration.
* **Ras:** Activates the MAPK pathway, which regulates gene expression and cell proliferation.
* **Calcium:** Increases intracellular calcium levels, triggering cytoskeletal rearrangements.
4. **Cytoskeletal Rearrangements:** The activated signaling pathways lead to the reorganization of the cytoskeleton, primarily actin filaments. This rearrangement involves the formation of filopodia, finger-like projections that extend towards the chemoattractant source.
5. **Cell Polarization:** The chemoattractant gradient induces polarization of the endothelial cell. The leading edge, facing the chemoattractant source, becomes enriched with receptors, signaling molecules, and adhesion molecules. The trailing edge, facing away from the chemoattractant, develops a retraction fiber.
6. **Adhesion and Migration:** The leading edge of the endothelial cell attaches to the extracellular matrix via integrins. Integrins are transmembrane receptors that connect the cytoskeleton to the extracellular matrix, providing traction for cell movement. As the cell migrates, the trailing edge detaches from the matrix and retracts.
7. **Proliferation and Tube Formation:** Once endothelial cells reach the target area, they proliferate and assemble into tube-like structures, forming new blood vessels. This process is regulated by growth factors and other signaling molecules involved in angiogenesis.
8. **Maturation and Remodeling:** Newly formed blood vessels undergo further maturation and remodeling to ensure proper function and integration into the existing vasculature. This involves recruitment of pericytes and smooth muscle cells, which provide structural support and regulate blood flow.'
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Protein | Definition | Taxonomy |
---|---|---|
GRB2-associated-binding protein 1 | A GRB2-associated-binding protein 1 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q13480] | Homo sapiens (human) |
Nuclear receptor subfamily 4 group A member 1 | A nuclear receptor subfamily 4 immunity group A member 1 that is encoded in the genome of human. [PRO:DNx, UniProtKB:P22736] | Homo sapiens (human) |
Vascular endothelial growth factor A | A vascular endothelial growth factor A, long form that is encoded in the genome of human. [PRO:DNx, UniProtKB:P15692] | Homo sapiens (human) |
Neuropilin-1 | A neuropilin-1 that is encoded in the genome of human. [PRO:WCB, UniProtKB:O14786] | Homo sapiens (human) |
Compound | Definition | Classes | Roles |
---|---|---|---|
4-phenylphenol | 4-phenylphenol: RN given refers to cpd without isomeric designation biphenyl-4-ol : A member of the class of hydroxybiphenyls that is biphenyl carrying a hydroxy group at position 4. | hydroxybiphenyls | |
4-phenylbenzoic acid | 4-phenylbenzoic acid: RN given refers to 4-carboxylic cpd | ||
celastrol | monocarboxylic acid; pentacyclic triterpenoid | anti-inflammatory drug; antineoplastic agent; antioxidant; EC 5.99.1.3 [DNA topoisomerase (ATP-hydrolysing)] inhibitor; Hsp90 inhibitor; metabolite | |
celastrol methyl ester | celastrol methyl ester: isolated from Tripterygium wilfordii; potent inhibitory activity on both Kir2.1 and ERG1 potassium channels, leading to LONG QT SYNDROME | carboxylic ester | |
alitretinoin | Alitretinoin: A retinoid that is used for the treatment of chronic hand ECZEMA unresponsive to topical CORTICOSTEROIDS. It is also used to treat cutaneous lesions associated with AIDS-related KAPOSI SARCOMA. | retinoic acid | antineoplastic agent; keratolytic drug; metabolite; retinoid X receptor agonist |
amentoflavone | biflavonoid; hydroxyflavone; ring assembly | angiogenesis inhibitor; antiviral agent; cathepsin B inhibitor; P450 inhibitor; plant metabolite | |
ala-thr-trp-leu-pro-pro-arg | |||
proanthocyanidin a1 | procyanidin A1: from aqueous extract of peanut skin; structure in first source | flavonoid oligomer | |
triptohypol C | triptohypol C : A pentacyclic triterpenoid with formula C29H40O4, originally isolated from the root bark of Tripterygium regelii. | benzenediols; monocarboxylic acid; pentacyclic triterpenoid | apoptosis inducer; plant metabolite |
cytosporone b | cytosporone B: a Nur77 agonist; structure in first source | aromatic ketone | |
pht 427 | 4-dodecyl-N-(1,3,4-thiadiazol-2-yl)benzenesulfonamide: an antineoplastic agent; structure in first source | ||
EG00229 | benzothiadiazole; dicarboxylic acid monoamide; L-arginine derivative; secondary carboxamide; sulfonamide; thiophenes | angiogenesis inhibitor; antineoplastic agent; neuropilin receptor antagonist | |
phosphomannopentaose sulfate | phosphomannopentaose sulfate: structure in first source |