RGD-dependent binding of TP508 to integrin αvβ3 mediates cell adhesion and induction of nitric oxide

Derkach, Dmitry N.; Wadekar, Subhagya A.; Perkins, Kim B.; Rousseau, Emma; Dreiza, Catherine M.; Cheung‐Flynn, Joyce; Ramos, Heidi C; Ugarova, Tatiana P.; Sheller, Michael R.

doi:10.1160/th09-07-0447

Cited by 3 publications

(1 citation statement)

References 43 publications

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“…While this is also the case for GelMA-cultured HUVECs, the increased NO levels are attributed to HUVEC-RGD interactions. RGD motifs have the potential to enhance NO production in HUVECs by activating the endothelial oxide synthase (eNOS) enzyme signalling pathway [68][69][70]. Additionally, RGD motifs can enhance the expression of the vascular endothelial growth factor (VEGF) [71][72][73], leading to an overall increase in angiogenic activity, which at the same time is associated with elevated NO levels.…”

Section: Discussionmentioning

confidence: 99%

Investigating multi-material hydrogel three-dimensional printing for in vitro representation of the neo-vasculature of solid tumours: a comprehensive mechanical analysis and assessment of nitric oxide release from human umbilical vein endothelial cells

et al. 2023

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Many solid tumours (e.g. sarcoma, carcinoma and lymphoma) form a disorganized neo-vasculature that initiates uncontrolled vessel formation to support tumour growth. The complexity of these environments poses a significant challenge for tumour medicine research. While animal models are commonly used to address some of these challenges, they are time-consuming and raise ethical concerns. In vitro microphysiological systems have been explored as an alternative, but their production typically requires multi-step lithographic processes that limit their production. In this work, a novel approach to rapidly develop multi-material tissue-mimicking, cell-compatible platforms able to represent the complexity of a solid tumour's neo-vasculature is investigated via stereolithography three-dimensional printing. To do so, a series of acrylate resins that yield covalently photo-cross-linked hydrogels with healthy and diseased mechano-acoustic tissue-mimicking properties are designed and characterized. The potential viability of these materials to displace animal testing in preclinical research is assessed by studying the morphology, actin expression, focal adhesions and nitric oxide release of human umbilical vein endothelial cells. These materials are exploited to produce a simplified multi-material three-dimensional printed model of the neo-vasculature of a solid tumour, demonstrating the potential of our approach to replicate the complexity of solid tumours in vitro without the need for animal testing.

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Section: Discussionmentioning

confidence: 99%

Investigating multi-material hydrogel three-dimensional printing for in vitro representation of the neo-vasculature of solid tumours: a comprehensive mechanical analysis and assessment of nitric oxide release from human umbilical vein endothelial cells

et al. 2023

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Peptide-based delivery to bone

Aoki

Alles

Soysa

et al. 2012

Advanced Drug Delivery Reviews

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Effect of Thrombin Fragment (TP508) on Myocardial Ischemia Reperfusion Injury in a Model of Type 1 Diabetes Mellitus

et al. 2010

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Background-We investigated the efficacy of novel thrombin fragment TP508 on ischemia-reperfusion injury using a porcine model of type 1 diabetes mellitus. Methods and Results-Alloxan-induced diabetic male Yucatan swine underwent 60 minutes of mid-left anterior descending coronary artery occlusion, followed by 120 minutes of reperfusion. Fifty minutes into ischemia, animals received either placebo (DM; nϭ8) or TP508 as a bolus of 1 mg/kg followed by infusion at 2.5 mg/kg per hour (DMT; nϭ8). Hemodynamic parameters and myocardial function were monitored. Monastryl blue/triphenyl tetrazolium chloride staining was used to assess sizes of the areas at risk and infarction. Coronary microvascular reactivity was measured and expression of cell survival and proapoptotic proteins quantified. Preoperative serum glucose values were similar between groups (309Ϯ57 mg/dL in DM versus 318Ϯ67 mg/dL in DMT; Pϭ0.92). Infarct size was smaller in the TP508-treated group (5.3Ϯ1.9% in DMT versus 19.4Ϯ5.6% in DM; Pϭ0.03). There was no statistically significant difference in global or regional left ventricular function between groups. Endothelium-dependent microvessel relaxation was moderately improved in the DMT group (Pϭ0.09), whereas endothelium-independent relaxation was similar between groups. The expression of cell survival proteins Akt, phospho-p38, and mammalian target of rapamycin was higher in the areas at risk of DMT animals compared with DM animals (PϽ0.05), and expressions of proapoptotic glycogen synthase kinase 3␤ and caspase 3 were lower in the DMT group (PϽ0.05). Conclusions-This study demonstrates that, in type 1 diabetic swine, TP508 reduces infarct size after ischemiareperfusion. Thus, TP508 may offer a novel approach in cardioprotection from ischemia-reperfusion injury in diabetic patients. (Circulation. 2010;122[suppl 1]:S162-S169.)

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RGD-dependent binding of TP508 to integrin αvβ3 mediates cell adhesion and induction of nitric oxide

Cited by 3 publications

References 43 publications

Investigating multi-material hydrogel three-dimensional printing for in vitro representation of the neo-vasculature of solid tumours: a comprehensive mechanical analysis and assessment of nitric oxide release from human umbilical vein endothelial cells

Investigating multi-material hydrogel three-dimensional printing for in vitro representation of the neo-vasculature of solid tumours: a comprehensive mechanical analysis and assessment of nitric oxide release from human umbilical vein endothelial cells

Peptide-based delivery to bone

Effect of Thrombin Fragment (TP508) on Myocardial Ischemia Reperfusion Injury in a Model of Type 1 Diabetes Mellitus

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