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Imaging Angiogenesis
Published in George C. Kagadis, Nancy L. Ford, Dimitrios N. Karnabatidis, George K. Loudos, Handbook of Small Animal Imaging, 2018
Tie2-Biotag mouse belongs to the most recent animal models that allow studying angiogenic signaling. This model is characterized by the expression of biotin ligase (BirA) under the control of the endothelial-specific Tie2 promoter. In this model, a cluster of BirA substrate sequences (Biotag) fused to a transmembrane domain can be targeted in vivo with highly specific avidinated imaging probes. As a result, biotinylated endothelial cells involved in angiogenesis can be imaged with a modality of choice using avidinated multimodal agents.
Angiogenesis and Roles of Adhesion Molecules in Psoriatic Disease
Published in Siba P. Raychaudhuri, Smriti K. Raychaudhuri, Debasis Bagchi, Psoriasis and Psoriatic Arthritis, 2017
Asmita Hazra, Saptarshi Mandal
The main angiogenic angiopoietin is Ang2, which causes vessel destabilization, initiation of angiogenesis, and transformation of capillaries into inflammatory venules, with increased leakiness and stickiness, in synergism with TNFα. Ang2 is expressed by endothelial cells near the VEGF-expressing epidermal keratinocytes in psoriasis lesions, and the vessel-stabilizing angiopoietin Ang1 is expressed by stromal cells in the vascularized papillary dermis of lesional skin. Their receptors Tie2 and Ang2 could also be upregulated in cultured dermal microvascular endothelial cell upon the addition of angiogenic factors like VEGF or FGF2. Successful antipsoriatic treatment was accompanied by a noticeable reduction of Ang2.
Vascular tumours and malformation
Published in Brice Antao, S Irish Michael, Anthony Lander, S Rothenberg MD Steven, Succeeding in Paediatric Surgery Examinations, 2017
Cameron C Trenor III, Steven J Fishman, Arin K Greene
RASA1 mutations cause capillary malformation–arteriovenous malformation; patients have cutaneous stains and arteriovenous malformations. PTEN mutations cause lipovascular hamartomas, atypical arteriovenous malformations without capillary stains as well as frontal bossing and penile freckling. VEGFR3 mutations can result in congenital lymphoedema. Mutations in TIE2 can cause sporadic venous malformations as well as hereditary cutaneomucosal lesions. FOXC2 mutations are responsible for lymphoedema–distichiasis syndrome; patients have congenital lymphoedema and a double row of eyelashes. Glomulin mutations cause glomuvenous malformations; lesions are small, bluish and painful. Endoglin mutations result in hereditary haemorrhagic telangiectasia. Mutations in KRIT1 are responsible for cerebral cavernous malformations. SOX18 mutations cause hypotrichosis–lymphoedema–telangiectasia syndrome.
Plasma thrombomodulin levels are associated with acute kidney injury in patients with acute heart failure
Published in Annals of Medicine, 2022
Shu-Min Lin, Chih-Hsiang Chang, Ting-Yu Lin, Allen Chung-Cheng Huang, Chiung-Hung Lin, Yung-Chang Chen, Pao-Hsien Chu
The site to which Ang-1 and Ang-2 bind is the same as that of the endothelial cell-specific Tie-2 receptor [14]. Ang-1 and Ang-2 are crucial to vascular development, maturation, and inflammation. After binding to the Tie-2 receptor, Ang-1 triggers the activation of Tie-2, whereas Ang-2 exerts an antagonistic response to Tie-2. Ang-1 is protective in its anti-inflammatory effects and stabilization of the endothelium, whereas Ang-2 promotes an inflammatory response by activating endothelial cells and enhancing vascular leakage [15]. The importance of angiopoietins in endothelial activation and injury to the vascular barrier has prompted extensive research into their role as biomarkers in critical illness [16]. Plasma Ang-2 levels are significantly higher in cases of acute heart failure than in healthy controls, making them a predictor of poor outcomes [17]. They are also an independent predictor of mortality in patients undergoing dialysis in intensive care units [18].
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).
Emerging drugs for the treatment of diabetic retinopathy
Published in Expert Opinion on Emerging Drugs, 2020
Elio Striglia, Andrea Caccioppo, Niccolò Castellino, Michele Reibaldi, Massimo Porta
Tie-2 is a transmembrane tyrosine-kinase receptor expressed in endothelial cells and its activation plays a role in inhibiting capillary leakage and suppressing inflammation and apoptosis in endothelial cells [48]. Tie-2 modulators exist in two isoforms [49]. In mice, angiopoietin-1 (Ang-1) has a protective effect in DR, suppressing VEGF-A induced neovascularization via Tie-2 activation [50], whereas Ang-2 exerts an opposite effect, promoting vascular inflammation and permeability, inducing pericyte apoptosis and BRB breakdown [51]. Pre-clinical research led to clinical application, showing the superiority of dual inhibition of VEGF-A and Ang-2 compared to VEGF-A inhibition alone [52]. In addition leukostasis plays a role of pivotal importance in the dysfunction of BRB in DR by the upregulation of reactive oxygen species and inflammatory cytokines. This pathological cycle causes the enhancement of vascular permeability [53].