VEGFD - Vascular Endothelial Growth Factor D | Elisa - Clia - Antibody - Protein

Background:

Vascular Endothelial Growth Factor D (VEGF-D) is a member of the vascular endothelial growth factor (VEGF) family, which plays a crucial role in angiogenesis, the formation of new blood vessels, and lymphangiogenesis, the formation of new lymphatic vessels. VEGF-D is a glycoprotein that shares structural similarities with other members of the VEGF family. It consists of multiple domains, including a central receptor-binding domain and N-terminal and C-terminal propeptides. VEGF-D primarily acts as a ligand for two receptors: VEGFR-2 (also known as KDR or Flk-1) and VEGFR-3 (Flt-4). Activation of these receptors by VEGF-D leads to signaling cascades that promote endothelial cell proliferation, migration, and survival, ultimately stimulating angiogenesis and lymphangiogenesis. VEGF-D is expressed in various tissues, including the lungs, heart, and skeletal muscle, as well as in certain tumors. Its expression can be induced by various factors, including hypoxia, inflammation, and growth factors. Dysregulation of VEGF-D signaling has been implicated in the pathogenesis of cardiovascular diseases such as atherosclerosis and pulmonary hypertension. Given its role in angiogenesis and lymphangiogenesis, VEGF-D and its receptors are potential targets for therapeutic intervention in various diseases, including cancer and cardiovascular disorders. Strategies aimed at modulating VEGF-D signaling are being explored for the development of novel therapies

Protein Structure:

• Composition: VEGFD is a secreted glycoprotein that undergoes proteolytic processing to become functionally active.
• Domains:
• Signal Peptide: Directs the protein to the secretory pathway.
• Receptor-Binding Domain: Allows binding to specific receptors.
• C-terminal Propeptide: Removed during proteolytic activation to produce the mature, active form of VEGFD.

Classification and Subtypes:

• Family: VEGFD belongs to the VEGF family, which also includes VEGFA, VEGFB, VEGFC, and placental growth factor (PlGF).
• Isoforms: Similar to VEGFC, VEGFD exists in different forms due to proteolytic processing, resulting in various isoforms with different receptor-binding affinities.

Function and Biological Significance:

• Lymphangiogenesis: VEGFD is crucial for the formation and maintenance of lymphatic vessels, playing a significant role in lymphangiogenesis by activating specific receptors on lymphatic endothelial cells.
• Angiogenesis: VEGFD also promotes the formation of blood vessels, contributing to angiogenesis.
• Role in Disease:
• Lymphedema: Although primarily VEGFC is linked to lymphedema, VEGFD also plays a role in lymphatic function and disorders.
• Cancer: VEGFD is implicated in cancer metastasis, particularly through the lymphatic system. Elevated levels of VEGFD are associated with increased lymphangiogenesis and metastatic potential in various cancers.
• Cardiovascular Diseases: VEGFD is involved in cardiovascular health, influencing blood vessel formation and function.

Interactions:

• Receptors: VEGFD primarily binds to VEGFR-3 (FLT4) and VEGFR-2 (KDR), similar to VEGFC. These interactions are critical for its role in lymphangiogenesis and angiogenesis.
• Proteolytic Activation: VEGFD undergoes proteolytic processing to convert from an inactive precursor to an active form capable of binding to its receptors.

Clinical Issues:

• Cancer Metastasis: Due to its role in promoting lymphangiogenesis and cancer cell dissemination through the lymphatic system, VEGFD is a target for anti-cancer therapies. Inhibitors of VEGFD or its receptors are being explored to prevent metastasis.
• Therapeutic Potential: Enhancing or inhibiting VEGFD signaling is being investigated for therapeutic applications. For example, promoting VEGFD activity could aid in lymphatic repair, while inhibiting it could prevent cancer metastasis.
• Cardiovascular Therapies: VEGFD's role in angiogenesis makes it a potential target for treating cardiovascular diseases that require new blood vessel formation.

Summary:

VEGFD (Vascular Endothelial Growth Factor D) is an essential member of the VEGF family, involved in lymphangiogenesis and angiogenesis. It undergoes proteolytic processing to become active and interacts mainly with VEGFR-3 and VEGFR-2 receptors. VEGFD plays a crucial role in the development and maintenance of the lymphatic system and blood vessels. Dysregulation of VEGFD is associated with diseases such as cancer metastasis and cardiovascular disorders. Understanding VEGFD's functions and mechanisms offers insights into potential therapeutic applications, including treating lymphatic and cardiovascular diseases and inhibiting cancer metastasis.