Early VEGFR2 activation in response to flow is VEGF-dependent and mediated by MMP activity

Paz, Nathaniel G. dela; Melchior, Benoît; Frangos, John A.

doi:10.1016/j.bbrc.2013.03.134

Cited by 19 publications

(13 citation statements)

References 31 publications

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“…; dela Paz et al . ). The lack of effect of passive movement induced hyperaemia on phosphorylation of the mechanosensor proteins could be related to the endothelial cells in vivo continuously experiencing large variations in shear stress according to heart cycle, muscle activation and changes in flow, and thus the increased flow during passive leg movement provides a relatively small stimulus.…”

Section: Discussionmentioning

confidence: 97%

Endothelial mechanotransduction proteins and vascular function are altered by dietary sucrose supplementation in healthy young male subjects

Gliemann

Rytter

Lindskrog

et al. 2017

The Journal of Physiology

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Endothelial mechanotransduction is important for vascular function but alterations and activation of vascular mechanosensory proteins have not been investigated in humans. In endothelial cell culture, simple sugars effectively impair mechanosensor proteins. To study mechanosensor- and vascular function in humans, 12 young healthy male subjects supplemented their diet with 3 × 75 g sucrose day for 14 days in a randomized cross-over design. Before and after the intervention period, the hyperaemic response to passive lower leg movement and active knee extensor exercise was determined by ultrasound doppler. A muscle biopsy was obtained from the thigh muscle before and after acute passive leg movement to allow assessment of protein amounts and the phosphorylation status of mechanosensory proteins and NADPH oxidase. The sucrose intervention led to a reduced flow response to passive movement (by 17 ± 2%) and to 12 W of active exercise (by 9 ± 1%), indicating impaired vascular function. A reduced flow response to passive and active exercise was paralleled by a significant up-regulation of platelet endothelial cell adhesion molecule (PECAM-1), endothelial nitric oxide synthase, NADPH oxidase and the Rho family GTPase Rac1 protein expression in the muscle tissue, as well as an increased basal phosphorylation status of vascular endothelial growth factor receptor 2 and a reduced phosphorylation status of PECAM-1. The phosphorylation status was not acutely altered with passive leg movement. These findings indicate that a regular intake of high levels of sucrose can impair vascular mechanotransduction and increase the oxidative stress potential, and suggest that dietary excessive sugar intake may contribute to the development of vascular disease.

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Section: Discussionmentioning

confidence: 97%

Endothelial mechanotransduction proteins and vascular function are altered by dietary sucrose supplementation in healthy young male subjects

Gliemann

Rytter

Lindskrog

et al. 2017

The Journal of Physiology

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“…For instance, pretreatment of primary bovine EC with a VEGFA neutralizing antibody does not inhibit flow-induced VEGR2 phosphorylation [51]. Conversely, other studies argue that VEGR2 activation by flow relies instead on a pool of VEGFA normally inaccessible, either bound within the extracellular matrix, or released either by flow stimulation by matrix metalloproteinases [52], or between EC in a juxtacrine manner [53]. In either case, shear stress-dependent VEGF signaling may be recalcitrant to anti-VEGFA therapies utilized clinically.…”

Section: Molecular and Cellular Consequences Of Choroidal Hemodynamicsmentioning

confidence: 99%

A Revised Hemodynamic Theory of Age-Related Macular Degeneration

Gelfand

Ambati

2016

Trends in Molecular Medicine

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Age-related macular degeneration (AMD) afflicts one out of every 40 individuals worldwide, causing irreversible central blindness in millions. The transformation of various tissue layers within the macula in the retina has led to competing conceptual models of the molecular pathways, cell types, and tissues responsible for the onset and progression of AMD. A model that has persisted for over 6 decades is the hemodynamic, or vascular theory of AMD progression, which states that vascular dysfunction of the choroid underlies AMD pathogenesis. Here, we re-evaluate this hypothesis in light of recent advances on molecular, anatomic, and hemodynamic changes underlying choroidal dysfunction in AMD. We propose an updated, detailed model of hemodynamic dysfunction as a mechanism of AMD development and progression.

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“…The shear stress will stimulate the proinflammatory response which is present on the surface of endothelial cells, increase the expression of endothelial adhesion molecules and their interactions with neutrophils, monocytes that triggers the release of IL-6. [23][24][25][26][27] Our study showed a higher release of IL-6 during pneumoperitoneum insufflation in the standard pressure group than in the low pressure group. Although CO 2 and surgical techniques can contribute to the release of proinflammatory cytokines, 28 our study showed that an acute, slight increase in intraabdominal pressure results in significantly increased IL-6 levels.…”

Section: Discussionmentioning

confidence: 48%

Effects of Low Versus Standard Pressure Pneumoperitoneum on Renal Syndecan-1 Shedding and VEGF Receptor-2 Expression in Living-donor Nephrectomy: A Randomized Controlled Study

Aditianingsih

Mochtar

Lydia

et al. 2020

Preprint

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Background Laparoscopic nephrectomy is a preferred technique for living kidney donation. However, positive-pressure pneumoperitoneum may have an unfavorable effect on the remaining kidney and other distant organs due to inflamed vascular endothelium and renal tubular cell injury in response to increased systemic inflammation. Early detection of vascular endothelial and renal tubular response is needed to prevent further kidney injury due to increased intraabdominal pressure induced by pneumoperitoneum. Transperitoneal laparoscopic living donor nephrectomy represented a human model of mild increasing intraabdominal pressure. This study aimed to assess the effect of increased intraabdominal pressure on vascular endothelium and renal tubular cells by comparing the effects of low and standard pressure pneumoperitoneum on vascular endothelial growth factor receptor-2 (VEGFR-2) expression and the shedding of syndecan-1 as the early markers to a systemic inflammation. Methods We conducted a prospective randomized study on 44 patients undergoing laparoscopic donor nephrectomy. Subjects were assigned to standard (12 mmHg) or low pressure (8 mmHg) groups. Baseline, intraoperative, and postoperative plasma interleukin-6, syndecan-1, and sVEGFR-2 were quantified by ELISA. Syndecan-1 and VEGFR-2 expression were assessed immunohistochemically in renal cortex tissue. Renal tubule and peritubular capillary ultrastructures were examined using electron microscopy. Perioperative hemodynamic changes, end-tidal CO2, serum creatinine, blood urea nitrogen, and urinary KIM-1 were recorded. Results The low pressure group showed lower intra- and postoperative heart rate, intraoperative plasma IL-6, sVEGFR-2 levels and plasma syndecan-1 than standard pressure group. Proximal tubule syndecan-1 expression was higher in the low pressure group. Proximal-distal tubules and peritubular capillary endothelium VEGFR-2 expression were lower in low pressure group. The low pressure group showed renal tubule and peritubular capillary ultrastructure with intact cell membranes, clear cell boundaries, and intact brush borders, while standard pressure group showed swollen nuclei, tenuous cell membrane, distant boundaries, vacuolizations, and detached brush borders. Conclusion The low pressure pneumoperitoneum attenuated the inflammatory response and resulted in reduction of syndecan-1 shedding and VEGFR-2 expression as the renal tubular and vascular endothelial proinflammatory markers to injury due to a systemic inflammation in laparoscopic nephrectomy. Trial registration ClinicalTrial.gov NCT:03219398, July 17th 2017. Keywords: pneumoperitoneum, renal resistive index, interleukin-6, syndecan-1, sVEGFR-2, laparoscopic nephrectomy

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Early VEGFR2 activation in response to flow is VEGF-dependent and mediated by MMP activity

Cited by 19 publications

References 31 publications

Endothelial mechanotransduction proteins and vascular function are altered by dietary sucrose supplementation in healthy young male subjects

Endothelial mechanotransduction proteins and vascular function are altered by dietary sucrose supplementation in healthy young male subjects

A Revised Hemodynamic Theory of Age-Related Macular Degeneration

Effects of Low Versus Standard Pressure Pneumoperitoneum on Renal Syndecan-1 Shedding and VEGF Receptor-2 Expression in Living-donor Nephrectomy: A Randomized Controlled Study

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