VEGF Blockade Inhibits Lymphocyte Recruitment and Ameliorates Immune-Mediated Vascular Remodeling

Zhang, Jiasheng; Silva, Teresa; Yarovinsky, Timur O.; Manes, Thomas D.; Tavakoli, Sina; Nie, Lei; Tellides, George; Pober, Jordan S.; Bender, Jeffrey R.; Sadeghi, Mehran M.

doi:10.1161/circresaha.109.210963

Cited by 56 publications

(70 citation statements)

References 50 publications

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“…Systemic VEGF acts as a vascular protective factor by stimulating antiapoptotic-signalling pathways to enhance endothelial integrity and maintain the antithrombogenic and anti-inflammatory properties of the endothelium (Tsurumi et al 1997;Zachary et al 2000). Furthermore, VEGF blockade is known to decrease the extravasation of circulating lymphocytes, which were shown to express a receptor for this cytokine (Sugita 2009;Zhang et al 2010). Systemic immune-mediated processes might be altered by the inhibition of VEGF.…”

Section: Discussionmentioning

confidence: 99%

Systemic levels of vascular endothelial growth factor before and after intravitreal injection of aflibercept or ranibizumab in patients with age‐related macular degeneration: a randomised, prospective trial

Zehetner

Kralinger

Modi

et al. 2014

Acta Ophthalmologica

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ABSTRACT.Purpose: To evaluate the changes of vascular endothelial growth factor (VEGF) plasma levels after intravitreal injections of aflibercept or ranibizumab in patients with exudative age-related macular degeneration (AMD). Methods: Thirty-eight patients with exudative AMD were included in this randomised, prospective study. Nineteen patients were randomised to treatment with intravitreal aflibercept (2.0 mg) and 19 to intravitreal ranibizumab (0.5 mg). The concentration of VEGF was measured by ELISA just before the injection, after 7 days and 1 month. Twenty-two age-and sex-matched healthy patients without chorioretinal diseases served as control. Results: The median baseline plasma VEGF concentration was 61.0 pg/ml in the control group, 43.0 pg/ml in the aflibercept group and 59.0 pg/ml in the ranibizumab group (p = 0.127). Seven days after intravitreal injection of aflibercept plasma levels were significantly reduced to values below the minimum detectable dose (MDD) in 17 of 19 patients (89.5%) resulting in a median VEGF concentration of <9 pg/ml (p < 0.001). The reduction persisted throughout 1 month with values below the MDD in 5 of 19 patients (26.3%) and a median measurement of 17.0 pg/ml (p < 0.001). In patients treated with ranibizumab no significant effects could be observed with a baseline VEGF of 59.0 pg/ml, 54.0 pg/ ml at 7 days (p = 0.776) and 58.5 pg/ml at 4 weeks of follow-up (p = 0.670). Conclusion: After intravitreal aflibercept injection, the systemic VEGF levels were significantly reduced throughout the observational period of 4 weeks. No significant systemic effects of intravitreal ranibizumab on plasma VEGF were observed.

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Section: Discussionmentioning

confidence: 99%

Systemic levels of vascular endothelial growth factor before and after intravitreal injection of aflibercept or ranibizumab in patients with age‐related macular degeneration: a randomised, prospective trial

Zehetner

Kralinger

Modi

et al. 2014

Acta Ophthalmologica

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“…45 As described above, several studies suggest that NGF can activate immunocompetent cells such as lymphocytes, macrophages and granulocytes. [27][28][29][30][31][32][33][34][35][36][37][38][39] Although several reports show the relationship between VEGF and inflammation, 46,47 to our knowledge there is no compelling evidence that VEGF directly activates immunocompetent cells. This difference in pro-inflammatory properties of growth factors might be one of the reasons for the discrepancy in transplant outcome.…”

Section: Do Not Distributementioning

confidence: 99%

Nerve growth factor is associated with islet graft failure following intraportal transplantation

Saito

Chan

Sakata

et al. 2012

Islets

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Nerve growth factor (NGF) has recently been recognized as an angiogenic factor with an important regulatory role in pancreatic b-cell function. We previously showed that treatment of pancreatic islets with NGF improved their quality and viability. Revascularization and survival of islets transplanted under the kidney capsule were improved by NGF. However, the usefulness of NGF in intraportal islet transplantation was not previously tested. To resolve this problem, we transplanted syngeneic islets (360 islet equivalents per recipient) cultured with or without NGF into the portal vein of streptozotocin-induced diabetic BALB/c mice. Analysis revealed that 44.4% (4/9) of control and 12.5% (1/8) of NGF-treated mice attained normoglycemia (# 200 mg/dL) (p = 0.195). NGF-treated islets led to worse graft function (area under the curve of intraperitoneal glucose tolerance tests (IPGTT) on post-operative day (POD) 30, control; 35,800 ± 3,960 min*mg/dl, NGF-treated; 47,900 ± 3,220 min*mg/dl: *p = 0.0348). NGF treatment of islets was also associated with increased graft failure [the percentage of TdT-mediated dUTP-biotin nick-end labeling (TUNEL)-positive and necrotic transplanted islets on POD 5, control; 23.8% (5/21), NGF-treated; 52.9% (9/17): p = 0.0650] following intraportal islet transplantation. Nonviable (TUNEL-positive and necrotic) islets in both groups expressed vascular endothelial growth factor (VEGF) and hypoxia-inducible factor-1a (HIF-1a). On the other hand, viable (TUNEL-negative and not necrotic) islets in both groups did not express VEGF and HIF-1a. In the present study, pre-transplant NGF treatment was associated with impaired survival and angiogenesis of intraportal islet grafts. The effect of NGF on islet transplantation may significantly vary according to the transplant site.

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“…10 Interrupting ICAM-1-LFA-1 ligation inhibits melanoma cell extravasation and metastases in a xenografted murine model. 23 By modulating tumor-endothelial interaction through the ICAM-1/LFA-1 pathway, bevacizumab could possibly interfere with the metastatic potential of Tleukemia/lymphoma.…”

Section: Discussionmentioning

confidence: 99%

Bevacizumab potentiates chemotherapeutic effect on T-leukemia/lymphoma cells by direct action on tumor endothelial cells

Wang¹,

Shi²,

Yang³

et al. 2011

Haematologica

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VEGF Blockade Inhibits Lymphocyte Recruitment and Ameliorates Immune-Mediated Vascular Remodeling

Cited by 56 publications

References 50 publications

Systemic levels of vascular endothelial growth factor before and after intravitreal injection of aflibercept or ranibizumab in patients with age‐related macular degeneration: a randomised, prospective trial

Systemic levels of vascular endothelial growth factor before and after intravitreal injection of aflibercept or ranibizumab in patients with age‐related macular degeneration: a randomised, prospective trial

Nerve growth factor is associated with islet graft failure following intraportal transplantation

Bevacizumab potentiates chemotherapeutic effect on T-leukemia/lymphoma cells by direct action on tumor endothelial cells

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