positive regulation of vascular endothelial cell proliferation

Definition

Target type: biologicalprocess

Any process that activates or increases the frequency, rate or extent of vascular endothelial cell proliferation. [GO_REF:0000058, GOC:BHF, GOC:BHF_telomere, GOC:nc, GOC:TermGenie, PMID:23201774]

Positive regulation of vascular endothelial cell proliferation is a critical process in angiogenesis, the formation of new blood vessels. It involves a complex interplay of signaling pathways, growth factors, and transcription factors that regulate the proliferation, migration, and differentiation of endothelial cells. Here is a detailed description of the biological process:

**1. Initiation and Stimulation:**
- **Growth factors:** Angiogenic growth factors, such as vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), and platelet-derived growth factor (PDGF), bind to their receptors on endothelial cells. This binding triggers intracellular signaling cascades that promote cell proliferation.
- **Hypoxia:** Low oxygen levels (hypoxia) stimulate the production of hypoxia-inducible factor (HIF), which activates the transcription of genes encoding angiogenic factors, including VEGF.

**2. Signal Transduction:**
- **Receptor tyrosine kinases (RTKs):** VEGF, FGF, and PDGF receptors are RTKs. Upon ligand binding, they become phosphorylated, activating downstream signaling pathways.
- **PI3K/AKT pathway:** Activated RTKs stimulate the phosphatidylinositol 3-kinase (PI3K) pathway, leading to the phosphorylation and activation of AKT. AKT promotes cell survival and proliferation, as well as inhibiting apoptosis.
- **MAPK pathway:** RTKs also activate the mitogen-activated protein kinase (MAPK) pathway. MAPK signaling promotes cell growth and proliferation by regulating the expression of genes involved in cell cycle progression.

**3. Transcriptional Regulation:**
- **HIF:** HIF binds to hypoxia-responsive elements (HREs) in the promoters of genes involved in angiogenesis, such as VEGF.
- **NF-κB:** Nuclear factor kappa B (NF-κB) is a transcription factor that is activated by pro-inflammatory cytokines. It promotes the expression of genes involved in angiogenesis, such as VEGF and IL-8.
- **Other transcription factors:** Other transcription factors, such as E2F1 and c-Myc, also play roles in regulating endothelial cell proliferation.

**4. Cell Cycle Progression:**
- **Cyclin-dependent kinases (CDKs):** Activated signaling pathways regulate the activity of CDKs, which control the progression of cells through the cell cycle.
- **Cell cycle checkpoints:** These checkpoints ensure that cells only progress through the cell cycle when conditions are favorable.

**5. Differentiation and Maturation:**
- **Endothelial cell differentiation:** Endothelial cell progenitors differentiate into mature endothelial cells, forming the lining of new blood vessels.
- **Maturation of new vessels:** The newly formed vessels undergo maturation, becoming more stable and integrated into the existing vasculature.

**6. Regulation and Feedback Mechanisms:**
- **Anti-angiogenic factors:** These factors, such as thrombospondin-1 and angiostatin, can inhibit angiogenesis.
- **Negative feedback loops:** Various mechanisms exist to regulate the balance between pro-angiogenic and anti-angiogenic signals, ensuring that angiogenesis is tightly controlled.

**7. Significance and Implications:**
- **Tissue repair and development:** Angiogenesis is essential for tissue repair, development, and wound healing.
- **Cancer:** Tumor growth and metastasis require angiogenesis. Anti-angiogenic drugs are used to inhibit tumor growth by targeting the pathways that promote angiogenesis.
- **Other diseases:** Abnormal angiogenesis contributes to various diseases, including cardiovascular diseases, inflammatory disorders, and age-related macular degeneration.

**8. Future Directions:**
- **Targeting specific pathways:** Further research aims to develop more effective and targeted anti-angiogenic therapies by targeting specific pathways involved in angiogenesis.
- **Understanding complex interactions:** A deeper understanding of the complex interplay between different signaling pathways, growth factors, and transcription factors involved in angiogenesis is crucial for developing new therapeutic strategies.'
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Proteins (11)

Compounds (931)