negative regulation of vascular endothelial cell proliferation

Definition

Target type: biologicalprocess

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

Negative regulation of vascular endothelial cell proliferation is a tightly controlled process that plays a crucial role in maintaining vascular homeostasis and preventing uncontrolled angiogenesis. It involves a complex interplay of signaling pathways, transcription factors, and cellular interactions that act to inhibit the growth and division of endothelial cells, the cells that line blood vessels. Key molecular mechanisms involved in this process include:

1. **Growth Factor Inhibition:**
- **VEGF Inhibition:** Vascular endothelial growth factor (VEGF) is a potent mitogen that stimulates endothelial cell proliferation. Negative regulation often involves reducing VEGF expression or blocking its signaling pathway. This can be achieved through mechanisms like:
- **Downregulation of VEGF production:** Various factors like hypoxia, transforming growth factor-beta (TGF-β), and other anti-angiogenic factors can suppress VEGF expression by inhibiting its transcription or translation.
- **Blocking VEGF receptors:** Soluble VEGF receptors or antibodies targeting VEGF receptors can prevent VEGF from binding and activating its downstream signaling pathways.

2. **Cell Cycle Arrest:**
- **Cyclin-dependent kinase (CDK) inhibition:** CDKs are enzymes crucial for cell cycle progression. Negative regulation can involve inhibiting CDK activity through:
- **Increased expression of CDK inhibitors:** Molecules like p21 and p27 can bind to and inhibit CDK activity, halting the cell cycle at specific checkpoints.
- **Induction of apoptosis:** If proliferation is uncontrolled, cells can undergo programmed cell death (apoptosis) to prevent excessive vessel growth. This can be triggered by factors like TNF-α, TRAIL, and caspase activation.

3. **Extracellular Matrix Modulation:**
- **Increased production of anti-angiogenic factors:** Molecules like thrombospondin-1, endostatin, and angiostatin can inhibit endothelial cell proliferation and migration by disrupting the extracellular matrix, hindering vessel formation.

4. **Immune Cell Regulation:**
- **Immune cell recruitment:** Some immune cells, like macrophages and T lymphocytes, can release anti-angiogenic factors and directly interact with endothelial cells, suppressing their proliferation.

5. **Microenvironmental Influences:**
- **Hypoxia:** Low oxygen levels can induce negative regulation, promoting the production of anti-angiogenic factors and inhibiting endothelial cell proliferation.
- **Shear stress:** Blood flow can induce shear stress on endothelial cells, which can activate signaling pathways that suppress proliferation.

These mechanisms work in concert to maintain a delicate balance, ensuring that new blood vessels are formed only when necessary and preventing excessive angiogenesis, which can contribute to diseases like cancer and macular degeneration.'
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Proteins (3)

Compounds (232)