Vascular Endothelial Growth Factor (VEGF)-A165-induced Prostacyclin Synthesis Requires the Activation of VEGF Receptor-1 and -2 Heterodimer

Neagoe, Paul‐Eduard; Lemieux, Carole; Sirois, Martin G.

doi:10.1074/jbc.m412017200

Cited by 113 publications

(88 citation statements)

References 54 publications

(84 reference statements)

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“…[7][8][9][10][11] Hypoxia and endothelial shear stress in HT are known to be major stimuli for sFLT-1 expression and release. [12][13][14][15][16] Furthermore, sFLT-1 is stimulated by the vascular sympathetic nervous system and has been reported to be elevated in patients with HT.…”

mentioning

confidence: 99%

Soluble fms-Like Tyrosine Kinase-1 and Endothelial Adhesion Molecules (Intercellular Cell Adhesion Molecule-1 and Vascular Cell Adhesion Molecule-1) as Predictive Markers for Blood Pressure Reduction After Renal Sympathetic Denervation

et al. 2014

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A rterial hypertension (HT) represents a major risk factor for cardiovascular morbidity and mortality.1 HT is associated with endothelial dysfunction that aggravates progressive vascular damage and atherosclerosis.2-4 Endothelial dysfunction can be indicated by elevated serum concentrations of endothelial adhesion molecules, including intercellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). 5,6 These adhesion molecules play important roles in accelerating atherosclerosis by attaching inflammatory cells to the vascular endothelial wall and promoting their subsequent migration through the endothelium.The vascular endothelial growth factor and its soluble receptor fms-like tyrosine kinase-1 (sFLT-1) are also associated with endothelial dysfunction, vascular remodeling, and endothelial repair and regeneration mechanisms.7-11 Hypoxia and endothelial shear stress in HT are known to be major stimuli for sFLT-1 expression and release.12-16 Furthermore, sFLT-1 is stimulated by the vascular sympathetic nervous system and has been reported to be elevated in patients with HT. The persistence of hypertensive blood pressure (BP) in patients with resistant hypertension is partially regulated by the renal sympathetic nerve system. 17-21 Renal sympathetic denervation (RSD) is an interventional treatment option for patients who have resistant hypertension, despite optimal medical treatment. 22,23 However, RSD is not effective in ≈8% to 12% of treated patients. 22,23 Predictive parameters regarding the response or nonresponse to RSD have not yet been described.We postulated a relationship among successful RSD-related BP reduction, endothelial dysfunction, and activated endothelial cells as indicated by ICAM-1, VCAM-1, and sFLT-1, specific markers for endothelial cell activity and hypertension-related endothelial sheer stress. Therefore, the primary aim of the present study was to examine the predictive value of sFlt-1, ICAM-1, and See Editorial Commentary, pp 907-908Abstract-Renal sympathetic denervation (RSD) is a treatment option for patients with resistant arterial hypertension, but in some patients it is not successful. Predictive parameters on the success of RSD remain unknown. The angiogenic factors soluble fms-like tyrosine kinase-1 (sFLT-1), intercellular cell adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) are known to be associated with endothelial dysfunction, vascular remodeling, and hypertension. We evaluated whether sFLT-1, ICAM-1, and VCAM-1 are predictive markers for blood pressure reduction after RSD. Consecutive patients (n=55) undergoing renal denervation were included. Venous serum samples for measurement of sFlt-1, ICAM-1, and VCAM-1 were collected before and 6 months after RSD. A therapeutic response was defined as an office systolic blood pressure reduction of >10 mm Hg 6 months after RSD. A significant mean office systolic blood pressure reduction of 31.2 mm Hg was observed in 46 patients 6 months after RSD. Nine patients were classified as...

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Soluble fms-Like Tyrosine Kinase-1 and Endothelial Adhesion Molecules (Intercellular Cell Adhesion Molecule-1 and Vascular Cell Adhesion Molecule-1) as Predictive Markers for Blood Pressure Reduction After Renal Sympathetic Denervation

et al. 2014

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“…In another in vitro model, the VEGF-dependent differentiation of a subset of human bone marrow-derived cells into vascular precursors, and subsequent proliferation of these cells, required the activation of a VEGFR-2/NRP-1-dependent signaling pathway (Fons et al, 2004). Finally, VEGF promotion of the synthesis and release of prostacyclin (PGI 2 ), an important mediator of angiogenesis, is thought to be mediated via NRP-1 binding (Neagoe et al, 2005). The angiogenic effects regulated through VEGF binding to NRP-2 are less well characterized and appear to be modulated differently from the effects controlled by NRP-1.…”

Section: Vegf Receptorsmentioning

confidence: 99%

Vascular endothelial growth factor in eye disease

Penn

Madan

Caldwell

et al. 2008

Progress in Retinal and Eye Research

636

527

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Collectively, angiogenic ocular conditions represent the leading cause of irreversible vision loss in developed countries. In the U.S., for example, retinopathy of prematurity, diabetic retinopathy and age-related macular degeneration are the principal causes of blindness in the infant, working age and elderly populations, respectively. Evidence suggests that vascular endothelial growth factor (VEGF), a 40 kDa dimeric glycoprotein, promotes angiogenesis in each of these conditions, making it a highly significant therapeutic target. However, VEGF is pleiotropic, affecting a broad spectrum of endothelial, neuronal and glial behaviors, and confounding the validity of anti-VEGF strategies, particularly under chronic disease conditions. In fact, among other functions VEGF can influence cell proliferation, cell migration, proteolysis, cell survival and vessel permeability in a wide variety of biological contexts. This article will describe the roles played by VEGF in the pathogenesis of retinopathy of prematurity, diabetic retinopathy and age-related macular degeneration. The potential disadvantages of inhibiting VEGF will be discussed, as will the rationales for targeting other VEGF-related modulators of angiogenesis.

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“…Pre-assembled heterodimer receptors of VEGFR-2 and VEGFR-3 subunits have been isolated from primary lymphatic endothelial cells 28,29 and detected in situ on angiogenic sprouts 30 . Heterodimerization between VEGFR-1 and VEGFR-2 subunits (VEGFR 1 − 2 ) has been detected in cell-free systems 13 and in endothelial cell lines 19,[31][32][33] . A computational model of VEGF receptor subunit dimerization concluded that a tenfold excess of one VEGF receptor subunit would result in minimal homodimerization of the less abundant receptor 34 .…”

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confidence: 99%

“…Therefore, dissection of VEGFR 1 − 2 heterodimerspecific function has been challenging. Receptor subunit knockdown and use of cell lines expressing specific receptors indicate that prostacyclin release 33 and biphasic calcium induction 32 is likely to be the result of VEGFR 1 − 2 activation.…”

mentioning

confidence: 99%

The role of heterodimerization between VEGFR-1 and VEGFR-2 in the regulation of endothelial cell homeostasis

et al. 2012

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Vascular Endothelial Growth Factor (VEGF)-A165-induced Prostacyclin Synthesis Requires the Activation of VEGF Receptor-1 and -2 Heterodimer

Cited by 113 publications

References 54 publications

Soluble fms-Like Tyrosine Kinase-1 and Endothelial Adhesion Molecules (Intercellular Cell Adhesion Molecule-1 and Vascular Cell Adhesion Molecule-1) as Predictive Markers for Blood Pressure Reduction After Renal Sympathetic Denervation

Soluble fms-Like Tyrosine Kinase-1 and Endothelial Adhesion Molecules (Intercellular Cell Adhesion Molecule-1 and Vascular Cell Adhesion Molecule-1) as Predictive Markers for Blood Pressure Reduction After Renal Sympathetic Denervation

Vascular endothelial growth factor in eye disease

The role of heterodimerization between VEGFR-1 and VEGFR-2 in the regulation of endothelial cell homeostasis

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