Page last updated: 2024-10-24

negative regulation of blood vessel endothelial cell proliferation involved in sprouting angiogenesis

Definition

Target type: biologicalprocess

Any process that stops, prevents or reduces the frequency, rate or extent of blood vessel endothelial cell proliferation involved in sprouting angiogenesis. [GO_REF:0000058, GOC:TermGenie, PMID:23388056]

Negative regulation of blood vessel endothelial cell proliferation involved in sprouting angiogenesis is a complex process that involves the coordinated action of various signaling pathways and regulatory factors. It plays a crucial role in maintaining vascular homeostasis and preventing uncontrolled angiogenesis, which can contribute to various pathological conditions such as tumor growth and diabetic retinopathy. Sprouting angiogenesis, a fundamental process of blood vessel formation, involves the migration and proliferation of endothelial cells from pre-existing vessels to form new capillaries. This process is tightly regulated by a delicate balance of pro-angiogenic and anti-angiogenic factors. Negative regulation of endothelial cell proliferation in this context acts as a brake on excessive vessel formation, ensuring proper vascular development and preventing pathological angiogenesis.

The process of negative regulation can be initiated by various signals and factors, including:

**1. Anti-angiogenic factors:** These molecules, such as angiostatin, endostatin, and thrombospondin-1, directly inhibit endothelial cell proliferation and migration. They act by interfering with key signaling pathways, such as the vascular endothelial growth factor (VEGF) pathway, and by inducing cell cycle arrest or apoptosis.

**2. Cell-cell interactions:** Endothelial cells communicate with each other through cell-cell adhesion molecules and signaling pathways. These interactions can regulate proliferation by sending inhibitory signals when cell density reaches a certain threshold.

**3. Extracellular matrix components:** The extracellular matrix (ECM) provides structural support and signaling cues to endothelial cells. Specific ECM components, such as heparin sulfate proteoglycans, can bind and sequester pro-angiogenic factors, reducing their availability to endothelial cells and inhibiting proliferation.

**4. Hypoxia-inducible factors (HIFs):** Hypoxia, or low oxygen levels, triggers the expression of HIFs, which in turn activate the expression of pro-angiogenic genes, including VEGF. However, HIFs can also induce the expression of anti-angiogenic factors, creating a feedback loop that limits excessive vessel formation.

**5. Immune cells:** Immune cells, particularly macrophages, play a role in regulating angiogenesis. Macrophages can release pro-angiogenic factors, such as VEGF, but they can also secrete anti-angiogenic factors, such as TNF-α and IFN-γ, depending on the microenvironment.

**6. Mechanical forces:** Blood flow and shear stress can influence endothelial cell proliferation and angiogenesis. Mechanical forces can activate signaling pathways that regulate cell growth and migration.

**7. Microenvironment:** The surrounding tissue environment, including the presence of other cell types, oxygen tension, and nutrient availability, can influence the balance of pro-angiogenic and anti-angiogenic factors, ultimately impacting endothelial cell proliferation.

**In summary, negative regulation of blood vessel endothelial cell proliferation in sprouting angiogenesis is a multifaceted process that involves a complex interplay of signaling pathways, regulatory factors, and environmental cues. It plays a vital role in maintaining vascular homeostasis and preventing uncontrolled angiogenesis, thereby contributing to overall tissue health and development.**'"

Proteins (1)

ProteinDefinitionTaxonomy
Tumor necrosis factor receptor superfamily member 16A tumor necrosis factor receptor superfamily member 16 that is encoded in the genome of human. [PRO:JAN, UniProtKB:P08138]Homo sapiens (human)

Compounds (3)

CompoundDefinitionClassesRoles
ale 0540ALE 0540: structure in first source
pd 90780PD 90780: a nonpeptide inhibitor of nerve growth factor; structure given in first source
2,3,4,10-tetrahydro-7,10-dimethyl-2,4-dioxobenzo(g)pteridineflavin