endothelial tube lumen extension

Definition

Target type: biologicalprocess

Any endothelial tube morphogenesis process by which the tube is increased in length. [GOC:dgh, PMID:23698350]

Endothelial tube lumen extension is a crucial step in vascular development and angiogenesis. It involves the coordinated actions of various cellular processes, including cell-cell adhesion, migration, and matrix remodeling. The process begins with the formation of a tubular network, where endothelial cells, the lining cells of blood vessels, assemble into cord-like structures. These cords then undergo lumenogenesis, the process of creating a hollow space within the cords. Lumen formation is driven by a combination of factors, including:

* **Cell-cell adhesion:** Endothelial cells express specialized adhesion molecules, such as vascular endothelial cadherin (VE-cadherin), that mediate cell-cell interactions. These interactions are essential for maintaining the integrity of the tubular structure.
* **Cell migration:** Endothelial cells migrate towards specific signals, such as vascular endothelial growth factor (VEGF), which promote angiogenesis. This migration is facilitated by the dynamic rearrangement of the actin cytoskeleton.
* **Matrix remodeling:** Endothelial cells secrete and remodel extracellular matrix proteins, such as collagen and laminin, which provide structural support for the developing lumen.

**The process of lumen extension involves the following steps:**

1. **Apical constriction:** Endothelial cells undergo apical constriction, a process where the apical surface of the cell shrinks, leading to a narrowing of the cell's lumenal space. This constriction is mediated by the actomyosin cytoskeleton and is regulated by various signaling pathways.
2. **Cavitation:** As cells undergo apical constriction, they create small cavities within the tubular structure. These cavities coalesce and expand, eventually forming a continuous lumen.
3. **Lumen enlargement:** The lumen continues to expand as endothelial cells migrate and remodel the extracellular matrix. This process is facilitated by the secretion of enzymes that degrade matrix proteins and by the insertion of new membrane into the lumenal surface of the cells.

**Regulation of lumen extension:**

Lumen extension is a tightly regulated process that is influenced by a complex interplay of signaling molecules, transcription factors, and cytoskeletal components. Some of the key regulatory factors include:

* **Vascular endothelial growth factor (VEGF):** VEGF is a potent angiogenic factor that promotes endothelial cell proliferation, migration, and lumen formation.
* **Notch signaling pathway:** Notch signaling plays a crucial role in regulating endothelial cell fate and lumen formation.
* **Rho GTPases:** Rho GTPases, such as Rac1 and RhoA, are involved in regulating the actin cytoskeleton and cell migration during lumen extension.
* **Integrins:** Integrins are cell adhesion receptors that connect the extracellular matrix to the intracellular cytoskeleton. They are essential for mediating cell-matrix interactions and regulating lumen formation.

**Clinical significance:**

Disruptions in the process of endothelial tube lumen extension can lead to various vascular pathologies, including vascular malformations, atherosclerosis, and tumor angiogenesis. Understanding the molecular mechanisms underlying this process is crucial for developing novel therapeutic strategies for treating these disorders.

**In summary, endothelial tube lumen extension is a complex and highly coordinated process that is essential for vascular development and angiogenesis. It involves the coordinated actions of cell-cell adhesion, migration, and matrix remodeling, and is regulated by a complex interplay of signaling molecules, transcription factors, and cytoskeletal components.**'"

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