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Chemopreventive Agents
Published in David E. Thurston, Ilona Pysz, 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).
Dopamine in the Immune and Hematopoietic Systems
Published in Nira Ben-Jonathan, 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.
Adult Stem Cells for Intervertebral Disc Repair
Published in Raquel M. Gonçalves, Mário Adolfo Barbosa, Gene and Cell Delivery for Intervertebral Disc Degeneration, 2018
Esther Potier, Delphine Logeart-Avramoglou
Risbud et al. (2007) provided evidence that the IVD also contains skeletal progenitor cells exhibiting the immunophenotype and the multidifferentiation potential typical of MSCs. Since then, various studies have validated the presence of IVD-derived MSCs (IVD-MSCs) in several species, such as human, pig, or rabbit (Blanco et al. 2010; Liu et al. 2011, 2014; Risbud et al. 2007; Sakai et al. 2012; Tao et al. 2013; Wang et al. 2016) (for a recent review, see Li et al. 2015). By selecting angiopoietin-1 receptor (Tie2)-positive cells, Sakai and collaborators further validated the presence of single-cell, highly proliferative, and multipotent progenitors in human, murine, and bovine NPs (Sakai et al. 2012; Tekari et al. 2016). Although MSCs could be derived from all IVD compartments (i.e., NP (Blanco et al. 2010; Risbud et al. 2007; Sakai et al. 2012; Tao et al. 2013; Wang et al. 2016), AF (Liu et al. 2014; Risbud et al. 2007; Wang et al. 2016), and end plates (Liu et al. 2011; Wang et al. 2016)), the perichondrium, a region in the outer zone of the AF and adjacent to the epiphyseal plate, has been proposed as the physiological niche of the IVD-MSCs (Henriksson et al. 2009a; Shi et al. 2015).
Novel nano-carriers with N-formylmethionyl-leucyl-phenylalanine-modified liposomes improve effects of C16-angiopoietin 1 in acute animal model of multiple sclerosis
Published in Drug Delivery, 2023
Xiao-Xiao Fu, Han Qu, Jing Wang, Hua-Ying Cai, Hong Jiang, Hao-Hao Chen, Shu Han
The fundamental events during the onset of acute EAE include extensive edema and cellular inflammation due to an impaired blood–brain barrier (BBB). Importantly, integrin αVβ3 permits endothelial cells to interact with many extracellular matrix proteins, including laminin. The synthesized peptide C16, a γ1 chain peptide of laminin-1, can selectively bind the αVβ3 and αVβ1 integrins in endothelial cells to block the interaction between leukocytes and endothelial cells, which ultimately inhibits the transmigration of inflammatory cells (Gaillard et al., 2012). A previous study has also verified that C16 had no effect on the total number of leukocytes, suggesting that C16 is not an immunosuppressant (Han S et al., 2010). As a member of the endothelial growth factor family, angiopoietin 1 (Ang-1) has important roles in the establishment and maintenance of the maturation, stabilization, and integrity of the vascular system (Fang et al., 2013). Moreover, C16 and Ang-1 can synergistically alleviate vascular leakage and inflammation and prevent the demyelination and axonal loss in the EAE rat model (Jiang et al., 2014). However, the solubility of C16 is largely affected by the pH of the solvent, which decreases its bioavailability and may limit its clinical application (Han et al., 2010).
The in vivo disposition of subcutaneous injected 14C-razuprotafib (14C-AKB-9778), a sulphamic acid phosphatase inhibitor, in nonclinical species and human
Published in Xenobiotica, 2021
Brandi Lynn Soldo, Patrick Camilleri, Akshay Buch, John Janusz
Razuprotafib is a first-in-class, small molecule Tie2 (tyrosine kinase with immunoglobulin-like and EGF-like domains 2) activator that works as a potent (IC50 = 0.017 nM) and selective inhibitor of VE-PTP (vascular endothelial-protein tyrosine phosphatase; aka HPTPβ), thereby enhancing Tie2 phosphorylation, activation, and signalling (Shen et al. 2014; Vestweber 2021). Tie2 is expressed principally in vascular endothelial cells and serves as the receptor for the angiopoietin family of secreted polypeptides. The Tie2/angiopoietin pathway has been identified as a key modulator of endothelial function and vascular stability (Peters et al. 2004; Thomas and August 2009; Saharinen et al. 2017). Activated Tie2 increases endothelial cell survival, adhesion, and cell junction integrity, thereby stabilising the vasculature. Razuprotafib is currently being developed to treat patients for vascular-related eye disease including the subcutaneous injection treatment of diabetic macular oedema and diabetic retinopathy (Campochiaro and Peters 2016) and as a topical drop treatment for ocular hypertension and open angle glaucoma (NCT04405245 2021).
Therapeutic approaches of trophic factors in animal models and in patients with spinal cord injury
Published in Growth Factors, 2020
María del Carmen Díaz-Galindo, Denisse Calderón-Vallejo, Carlos Olvera-Sandoval, J. Luis Quintanar
Blood spinal cord barrier (BSCB) is formed by the spinal capillaries and it is responsible for regulating the molecules that can enter the tissue, protecting it from the neurotoxins in the systemic circulation . In fact, one of the first events after SCI is the alteration of the BSCB which is very detrimental for tissue recovery. A recent study revealed that 48 h after SCI, the permeability of BSCB increased significantly in the untreated mice compared to mice treated with intraperitoneal melatonin. In addition, it was found that melatonin can improve and restore the integrity of BSCB by regulating tight junction proteins (Wu et al. 2014). In another study, Jing et al. (2014) investigated the effect of melatonin on microvessels after SCI. In this study, they found that melatonin improved blood loss, possibly due to positive regulation of angiopoietin-1 in the pericytes. Angiopoietin-1 can attenuate inflammation and apoptosis and protect microvessels by increasing the coverage of pericytes. Therefore, the neuroprotective effects of melatonin can also be derived from its ability to promote repair of BSCB.