regulation of blood vessel endothelial cell proliferation involved in sprouting angiogenesis

Definition

Target type: biologicalprocess

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

Sprouting angiogenesis is a crucial process in the formation of new blood vessels from pre-existing ones and is tightly regulated by a complex interplay of signaling pathways, growth factors, and extracellular matrix components. This process is essential for normal development, wound healing, and tissue repair.

The process of sprouting angiogenesis is initiated by a stimulus, such as hypoxia (low oxygen levels), which triggers the expression of pro-angiogenic factors like vascular endothelial growth factor (VEGF). VEGF binds to its receptors (VEGFRs) on the surface of endothelial cells, leading to their activation and triggering a cascade of intracellular signaling events.

These signals promote endothelial cell proliferation, migration, and the formation of new blood vessels.

**Endothelial Cell Proliferation:**
- The activation of VEGFRs triggers downstream signaling pathways, including the PI3K/AKT and MAPK pathways.
- These pathways stimulate cell cycle progression and DNA synthesis, promoting the proliferation of endothelial cells.
- Other growth factors like fibroblast growth factor (FGF) and platelet-derived growth factor (PDGF) also contribute to endothelial cell proliferation by activating their respective receptors.

**Endothelial Cell Migration:**
- Activated endothelial cells begin to migrate towards the source of the angiogenic stimulus, guided by chemoattractants like VEGF and other growth factors.
- Cell migration involves the rearrangement of the cytoskeleton, driven by the activation of Rho GTPases and other signaling pathways.
- Endothelial cells also secrete proteolytic enzymes like matrix metalloproteinases (MMPs) that degrade the extracellular matrix, allowing them to move through the surrounding tissues.

**Formation of Sprouting Blood Vessels:**
- As endothelial cells proliferate and migrate, they form tubular structures known as sprouts.
- These sprouts extend towards the angiogenic stimulus, guided by chemoattractants and other guidance cues.
- Sprouting is accompanied by the recruitment of pericytes, which are smooth muscle-like cells that wrap around the newly formed vessels, providing structural support and regulating blood flow.

**Maturation of New Vessels:**
- Once the sprouts reach their destination, they connect with existing blood vessels, forming a continuous network.
- The newly formed vessels undergo maturation, including the deposition of basement membrane and the recruitment of pericytes, which stabilize the vessel structure.

The regulation of sprouting angiogenesis is a complex and finely tuned process involving a balance between pro-angiogenic and anti-angiogenic factors. Dysregulation of this process can contribute to various pathological conditions, including cancer, diabetic retinopathy, and atherosclerosis.'
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Proteins (1)

Compounds (3)