Angiogenesis

Angiogenesis is a complex process in which new blood vessels develop from existing capillaries, eventually forming a complete, regular and mature vascular network. This process involves the degradation of the basement membrane and the activation, proliferation and migration of endothelial cells (EC), and is regulated by various pro-angiogenic and anti-angiogenic factors. In some diseases, angiogenesis becomes disordered and excessive due to the overexpression of angiogenic factors and the inactivation of anti-angiogenic factors. Additionally, angiogenesis also promotes the development of autonomous blood supply in the tumor microenvironment (TME), thereby contributing to the progression of various malignant tumors.

The balance between these pro- and anti-angiogenic factors determines whether new blood vessels will form, regress, or remain stable. Common pro-angiogenic factors include vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), angiopoietin (Ang), platelet-derived growth factor (PDGF), transforming growth factor-beta (TGF-β), etc. These factors bind receptors on endothelial cells, triggering signal transduction of various pathways such as PI3K/Akt, Erk1/2, Smad, and Notch, thereby leading to the proliferation and migration of endothelial cells.

In the process of angiogenesis, beyond the primary contributing factors, various other biomolecules also play crucial auxiliary roles in the coordinated operation of the complex process of angiogenesis. In-depth research into the functions of these biomolecules in angiogenesis would contribute to the development of new therapeutic strategies and a deep understanding of disease mechanisms. Amerigo Scientific provides high-purity inhibitors, agonists, and antagonists specifically targeting these biomolecules involved in angiogenesis.

Product Range

Targeting Bruton tyrosine kinase (BTK)

BTK is a key signaling molecule of the B-cell receptor signaling complex that plays an important role in the development and maturation of malignant B cells. It mediates signal transduction initiated by the B-cell receptor (BCR) and IL-5 receptor. In addition, BTK is expressed in various cells within the tumor microenvironment, including tumor-associated macrophages (TAMs) and endothelial cells. Its activation contributes to the production of pro-angiogenic factors and promotes endothelial cell migration and tube formation. BTK inhibitors bind to BTK to block its activity, thereby preventing BTK-mediated pro-angiogenic signaling.

Targeting Hypoxia-inducible factors (HIFs)

HIFs are transcriptional regulators that enable cells to adapt to low oxygen levels, a common feature of the tumor microenvironment. Under hypoxic conditions, HIF-1α and HIF-2α subunits become stabilized and translocate to the nucleus, where they activate the transcription of a number of genes, including many that are critical for angiogenesis. HIF prolyl hydroxylases (PHDs) are enzymes that play a crucial role in regulating HIF activity, and they act as oxygen sensors by hydroxylating specific proline residues on the HIF protein.

In angiogenesis, HIFs are potent inducers of VEGF expression, thus linking hypoxia to the initiation of angiogenesis. They also regulate the expression of other pro-angiogenic factors, such as Ang-2 and placental growth factor (PlGF), as well as enzymes involved in extracellular matrix remodeling. The role of HIFs in tumor angiogenesis makes them a highly attractive therapeutic target.

Targeting Integrins

Integrins are a family of transmembrane receptors that mediate cell-matrix and cell-cell interactions. On endothelial cells, certain integrins, such as αvβ3 and αvβ5 , play crucial roles in angiogenesis by providing traction for migrating cells and by transducing signals that regulate cell survival, proliferation, and differentiation.

During angiogenesis, the interaction of these integrins with extracellular matrix components, such as vitronectin and fibronectin, is essential for the adhesion and migration of endothelial cells as they form new vessel sprouts. In addition, integrin signaling also crosstalks with the VEGF pathway. The specific expression of some integrins on angiogenic blood vessels enables them potential targets for anti-cancer therapies.

Targeting Protease-activated receptors (PARs)

PARs are a class of G protein-coupled receptors that are activated by proteolytic cleavage of their extracellular domain. This cleavage unmasks a tethered ligand that binds to and activates the receptor. Proteases like thrombin and trypsin are key activators of PARs, and they are often present in the tumor microenvironment.

PAR1 and PAR2 are the most implicated members of this family in angiogenesis. Their activation on endothelial cells can induce the expression of pro-angiogenic factors like VEGF, promote endothelial cell proliferation and migration, and increase vascular permeability.

Targeting Others

Amerigo Scientific also offers products that act on other factors involved in angiogenesis, for use in biomedical research, particularly in the development of cancer treatment, the study of inflammatory responses, and the research on the mechanisms of angiogenesis-related diseases.