Dopamine in the Immune and Hematopoietic Systems
Nira Ben-Jonathan in Dopamine, 2020
Angiogenesis is a highly regulated process that takes place through two nonexclusive events of microvascular growth: sprouting or splitting [70]. Sprouting differs from splitting angiogenesis by forming entirely new vessels as opposed to splitting existing vessels. As illustrated in Figure 9.6, sprouting proceeds in several well-characterized stages. First, angiogenic factors [VEGF and fibroblast growth factor (FGF)], released from neighboring cells, bind to their respective receptors on endothelial cells and activate signal transduction pathways. Matrix metalloproteinases (MMPs), produced by the endothelial cells are then activated and degrade the extracellular matrix, enabling an escape of endothelial cells from the parental vessel walls. This is followed by their migration and proliferation. The integrins, expressed by endothelial cells, facilitate their adhesion to the extracellular matrix and the formation of solid sprouts that connect to neighboring vessels. Angiopoietin 1 (Ang-1), binding to Tie-2 receptors, stimulates pericyte recruitment and vessel stabilization. Final vessel maturation and stabilization necessitate additional morphological changes that include lumen formation and perfusion, network establishment, remodeling, and pruning to become full-fledged functional vessels.
Pulmonary Endothelium in Health and Viral Infections
Sunit K. Singh in Human Respiratory Viral Infections, 2014
Four members have been identified in the angiopoietin family. Three of these members, angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2), and angiopoietin-4 (Ang-4) are expressed in humans. Ang-1 is an oligomeric-secreted glycoprotein that exerts its effects through the receptor TIE2, an endothelial-specific tyrosine kinase. The basic functions of Ang-1 are induction of EC migration, formation of capillary-like structures, inhibition of EC apoptosis, reduction of vascular permeability, and inflammation and maintenance of vascular integrity.38 The expression of Ang-1 and TIE2 is present during development of blood vessels. Ang-1 is expressed and secreted by vascular SMCs, while TIE2 is a transmembrane receptor expressed in ECs. In the adult lung vasculature, Ang-1 expression is reduced significantly, showing minimal presence,57 while the expression of TIE2 remains unaltered.57,58 The second member of the angiopoietin family, Ang-2, is a TIE2 receptor agonist or, mainly, antagonist. Both Ang-1 and Ang-2 appear to have the same affinity for TIE2. Ang-2, however, has a context-specific effect depending on the cell type and condition. In the presence of Ang-1 (i.e., a TIE2 agonist), Ang-2 will mostly act as an antagonist and block TIE2 signaling, preventing cytoprotection. Activation of Ang-2/TIE2 signaling promotes vascular destabilization and VEGF-induced angiogenesis.58,59
Chemopreventive Agents
David E. Thurston, Ilona Pysz in Chemistry and Pharmacology of Anticancer Drugs, 2021
Angiogenesis is the process underlying the formation and development of new blood vessels vital for the growth and development of new cells, as in wound healing. However, it also plays an important role in tumor growth, development, and metastasis, as it facilitates the transport of oxygen and nutrients to a growing tumor and the removal of waste products through the formation of a supporting vascular network. Angiogenesis is controlled by growth factors such as VEGF, TGF-α, TGF-β, TNF-α, angiogenin, IL-8, and the angiopoietins. One of the primary regulators of tumor angiogenesis is the pro-angiogenic factor VEGF, a potent endothelial cell-specific mitogen which stimulates endothelial cell growth originating in arteries, veins, and lymph drainage vessels (Figure 12.5).
Growth factor signaling pathways in vascular development and disease
Published in Growth Factors, 2019
Angiopoietin signaling has complex, context-specific roles in regulating blood vessel growth and has a central role in maintaining vessel stability (Saharinen, Eklund, and Alitalo 2017). The ligands angiopoietin 1 (ANGPT1) and ANGPT2 signal through two tyrosine kinase receptors: tyrosine kinase with immunoglobulin-like and EGF-like domains 1 (TIE1) and TIE2 (TEK) (Saharinen, Eklund, and Alitalo 2017). TIE1 is an orphan receptor normally required for full activation of TIE2 (Korhonen et al. 2016). ANGPT1 is a constitutive agonist of TIE2 and is largely responsible for basal TIE2 activation, promoting EC quiescence and vessel stabilization. In part, ANGPT1/TIE2 achieves this by activating PI3K/AKT signaling, which phosphorylates and expels the Forkhead box O (FOXO) transcription factor FOXO1 from the nucleus. This prevents FOXO1 from promoting the expression of vascular destabilizing genes, which includes ANGPT2 (Daly et al. 2004) (Figure 2). ANGPT2 acts predominantly as a competitive inhibitor of ANGPT1, preventing TIE2 activation (Maisonpierre et al. 1997). In some contexts, ANGPT2 can be a weak agonist (Saharinen, Eklund, and Alitalo 2017) but the physiological relevance of this is not always clear (Mueller and Kontos 2016). ANGPT2 inhibition of TIE2 weakens EC-EC junctions, causing vascular destabilization (Saharinen et al. 2008).
Diabetic retinopathy: a complex pathophysiology requiring novel therapeutic strategies
Published in Expert Opinion on Biological Therapy, 2018
Michael Whitehead, Sanjeewa Wickremasinghe, Andrew Osborne, Peter Van Wijngaarden, Keith R. Martin
The angiopoietin family is involved in the regulation of vascular maturation and neovascularization. Angiopoietin-1 and -2 (Ang1 and 2) are known to have opposing effects when binding to their cognate receptor, the receptor tyrosine kinase Tie2. Ang1 induces Tie2 activation and phosphorylation, thereby promoting vessel stabilization and maturation. In addition, Ang1 has demonstrated anti-inflammatory effects and the ability to inhibit leukocyte adhesion to endothelial cells in animal models [92,93]. By contrast, Ang2 is a context-dependent mediator of the Tie2 pathway and can act as a mild agonist or an antagonist of the receptor. To dephosphorylate and thereby deactivate the Tie2 receptor, Ang2 activates protein tyrosine phosphatase beta or vascular endothelial PTP, which in turn leads to blood vessel destabilization. This destabilization is essential for the normal process of angiogenesis but can lead to endothelial cell apoptosis in the absence of VEGF signaling [94,95].
Predicting the likelihood of bronchopulmonary dysplasia in premature neonates
Published in Expert Review of Respiratory Medicine, 2019
Patrick A Philpot, Vineet Bhandari
Other biomarkers for BPD include type IV collagen, cluster of differentiation (CD) 9, the C-terminal fragment of Type 1 collagen, and soluble L-selectin and have been previously reviewed [4]. These factors have all been shown to be decreased in the serum of infants who develop BPD. On the other hand, E-selectin, eosinophilic cationic protein, and 8-isoprostanes are all increased in infants with BPD [4]. These markers are likely involved in the vascular dysregulation that helps define the BPD phenotype. The angiopoietin (Ang)/Tie-2 ligand/receptor pathway interacts with the vascular endothelial growth factor (VEGF) pathway to aid the development of blood vessels during angiogenesis. Low concentrations of the proangiogenic Ang-1 and the high concentration of the antiangiogenic endostatin in cord blood have been found to be predictive of subsequent BPD as noted previously. VEGF and the proangiogenic factor platelet-derived growth factor-BB (PDGF BB) were significantly elevated in blood at 5 days of life in infants who later developed the ‘new’ BPD [32]. The antiangiogenic endothelial monocyte activating polypeptide II (EMAP II), which downregulates VEGFR2 phosphorylation, has also been hypothesized to play a role in BPD pathogenesis.
Related Knowledge Centers
- Angiogenesis
- Growth Factor
- Peptide
- Receptor Tyrosine Kinase
- Smooth Muscle
- Vascular Endothelial Growth Factor
- Cytokine
- N-Terminus
- C-Terminus
- Tie1