References of "Lambert, Vincent"
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See detailBone marrow-derived mesenchymal cells and MMP13 contribute to experimental choroidal neovascularization.
Lecomte, Julie ULg; Louis, Krystel; Detry, Benoît ULg et al

in Cellular and Molecular Life Sciences : CMLS (2011), 68

In this study, we evaluate the potential involvement of collagenase-3 (MMP13), a matrix metalloproteinase (MMP) family member, in the exudative form of age-related macular degeneration characterized by a ... [more ▼]

In this study, we evaluate the potential involvement of collagenase-3 (MMP13), a matrix metalloproteinase (MMP) family member, in the exudative form of age-related macular degeneration characterized by a neovascularisation into the choroid. RT-PCR analysis revealed that human neovascular membranes issued from patients with AMD expressed high levels of Mmp13. The contribution of MMP13 in choroidal neovascularization (CNV) formation was explored by using a murine model of laser-induced CNV and applying it to wild-type mice (WT) and Mmp13-deficient mice (Mmp13 ( -/- ) mice). Angiogenic and inflammatory reactions were explored by immunohistochemistry. The implication of bone marrow (BM)-derived cells was determined by BM engraftment into irradiated mice and by injecting mesenchymal stem cells (MSC) isolated from WT BM. The deficiency of Mmp13 impaired CNV formation which was fully restored by WT BM engraftment and partially rescued by several injections of WT MSC. The present study sheds light on a novel function of MMP13 during BM-dependent choroidal vascularization and provides evidence for a role for MSC in the pathogenesis of CNV. [less ▲]

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See detailMicroRNA-21 Exhibits Antiangiogenic Function by Targeting RhoB Expression in Endothelial Cells.
Sabatel, Céline; Malvaux, Ludovic ULg; Bovy, Nicolas ULg et al

in PLoS ONE (2011), 6(2), 16979

BACKGROUND: MicroRNAs (miRNAs) are endogenously expressed small non-coding RNAs that regulate gene expression at post-transcriptional level. The recent discovery of the involvement of these RNAs in the ... [more ▼]

BACKGROUND: MicroRNAs (miRNAs) are endogenously expressed small non-coding RNAs that regulate gene expression at post-transcriptional level. The recent discovery of the involvement of these RNAs in the control of angiogenesis renders them very attractive in the development of new approaches for restoring the angiogenic balance. Whereas miRNA-21 has been demonstrated to be highly expressed in endothelial cells, the potential function of this miRNA in angiogenesis has never been investigated. METHODOLOGY/PRINCIPAL FINDINGS: We first observed in endothelial cells a negative regulation of miR-21 expression by serum and bFGF, two pro-angiogenic factors. Then using in vitro angiogenic assays, we observed that miR-21 acts as a negative modulator of angiogenesis. miR-21 overexpression reduced endothelial cell proliferation, migration and the ability of these cells to form tubes whereas miR-21 inhibition using a LNA-anti-miR led to opposite effects. Expression of miR-21 in endothelial cells also led to a reduction in the organization of actin into stress fibers, which may explain the decrease in cell migration. Further mechanistic studies showed that miR-21 targets RhoB, as revealed by a decrease in RhoB expression and activity in miR-21 overexpressing cells. RhoB silencing impairs endothelial cell migration and tubulogenesis, thus providing a possible mechanism for miR-21 to inhibit angiogenesis. Finally, the therapeutic potential of miR-21 as an angiogenesis inhibitor was demonstrated in vivo in a mouse model of choroidal neovascularization. CONCLUSIONS/SIGNIFICANCE: Our results identify miR-21 as a new angiogenesis inhibitor and suggest that inhibition of cell migration and tubulogenesis is mediated through repression of RhoB. [less ▲]

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See detailMir-146a : A new angiostatic miRNA with tumor-suppressive properties
Halkein, Julie ULg; Castermans, Karolien; Malvaux, Ludovic et al

Poster (2010, October)

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See detailInvolvement of miR-125b in in vitro and in vivo angiogenesis
Malvaux, Ludovic; Pendeville, Hélène; Sabatel, Céline et al

Poster (2010, May 21)

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See detailStudy of the role of miR-21 in the regulation of angiogenesis
Sabatel, Céline; Malvaux, Ludovic; Bovy, Nicolas ULg et al

Poster (2010, May)

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See detailStudy of the role of miR-21 in the regulation of angiogenesis
Sabatel, Céline; Malvaux, Ludovic; Bovy, Nicolas ULg et al

Poster (2010, March)

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See detailInvolvement of miR-125b in in vitro and in vivo angiogenesis
Malvaux, Ludovic; Pendeville, Hélène; Sabatel, Céline et al

Poster (2010, March)

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See detailDoes plasminogen activator inhibitor-1 drive lymphangiogenesis?
Bruyere, Francoise; Melen-Lamalle, Laurence; Blacher, Silvia ULg et al

in PLoS ONE (2010), 5(3), 9653

The purpose of this study is to explore the function of plasminogen activator inhibitor-1 (PAI-1) during pathological lymphangiogenesis. PAI-1, the main physiological inhibitor of plasminogen activators ... [more ▼]

The purpose of this study is to explore the function of plasminogen activator inhibitor-1 (PAI-1) during pathological lymphangiogenesis. PAI-1, the main physiological inhibitor of plasminogen activators is involved in pathological angiogenesis at least by controlling extracellular proteolysis and by regulating endothelial cell survival and migration. Protease system's role in lymphangiogenesis is unknown yet. Thus, based on its important pro-angiogenic effect, we hypothesized that PAI-1 may regulate lymphangiogenesis associated at least with metastatic dissemination of cancer cells. To address this issue, we studied the impact of PAI-1 deficiency in various murine models of tumoral lymphangiogenesis. Wild-type PAI-1 proficient mice were used as controls. We provide for the first time evidence that PAI-1 is dispensable for tumoral lymphangiogenesis associated with breast cancers either induced by mammary carcinoma cell injection or spontaneously appearing in transgenic mice expressing the polyomavirus middle T antigen (PymT) under the control of a mouse mammary tumor virus long-terminal repeat promoter (MMTV-LTR). We also investigated inflammation-related lymphatic vessel recruitment by using two inflammatory models. PAI-1 deficiency did neither affect the development of lymphangioma nor burn-induced corneal lymphangiogenesis. These novel data suggest that vascular remodelling associated with lymphangiogenesis and angiogenesis involve different molecular determinants. PAI-1 does not appear as a potential therapeutic target to counteract pathological lymphangiogenesis. [less ▲]

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See detailADAMTS-2 functions as anti-angiogenic and anti-tumoral molecule independently of its catalytic activity.
Dubail, Johanne ULg; Kesteloot, F.; Deroanne, Christophe ULg et al

in Cellular & Molecular Life Sciences (2010)

ADAMTS-2 is a metalloproteinase that plays a key role in the processing of fibrillar procollagen precursors into mature collagen molecules by excising the amino-propeptide. We demonstrate that recombinant ... [more ▼]

ADAMTS-2 is a metalloproteinase that plays a key role in the processing of fibrillar procollagen precursors into mature collagen molecules by excising the amino-propeptide. We demonstrate that recombinant ADAMTS-2 is also able to reduce proliferation of endothelial cells, and to induce their retraction and detachment from the substrate resulting in apoptosis. Dephosphorylation of Erk1/2 and MLC largely precedes the ADAMTS-2 induced morphological alterations. In 3-D culture models, ADAMTS-2 strongly reduced branching of capillary-like structures formed by endothelial cells and their long-term maintenance and inhibited vessels formation in embryoid bodies (EB). Growth and vascularization of tumors formed in nude mice by HEK 293-EBNA cells expressing ADAMTS-2 were drastically reduced. A similar anti-tumoral activity was observed when using cells expressing recombinant deleted forms of ADAMTS-2, including catalytically inactive enzyme. Nucleolin, a nuclear protein also found to be associated with the cell membrane, was identified as a potential receptor mediating the antiangiogenic properties of ADAMTS-2. [less ▲]

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See detailFurther pharmacological and genetic evidence for the efficacy of PlGF inhibition in cancer and eye disease.
Van de Veire, Sara; Stalmans, Ingeborg; Heindryckx, Femke et al

in Cell (2010), 141(1), 178-90

Our findings that PlGF is a cancer target and anti-PlGF is useful for anticancer treatment have been challenged by Bais et al. Here we take advantage of carcinogen-induced and transgenic tumor models as ... [more ▼]

Our findings that PlGF is a cancer target and anti-PlGF is useful for anticancer treatment have been challenged by Bais et al. Here we take advantage of carcinogen-induced and transgenic tumor models as well as ocular neovascularization to report further evidence in support of our original findings of PlGF as a promising target for anticancer therapies. We present evidence for the efficacy of additional anti-PlGF antibodies and their ability to phenocopy genetic deficiency or silencing of PlGF in cancer and ocular disease but also show that not all anti-PlGF antibodies are effective. We also provide additional evidence for the specificity of our anti-PlGF antibody and experiments to suggest that anti-PlGF treatment will not be effective for all tumors and why. Further, we show that PlGF blockage inhibits vessel abnormalization rather than density in certain tumors while enhancing VEGF-targeted inhibition in ocular disease. Our findings warrant further testing of anti-PlGF therapies. [less ▲]

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See detailNew Biological Investigations on 3-Bromophenyl 6-Acetoxymethyl-2-oxo-2H-1-Benzopyran-3-Carboxylate as Anti-angiogenic Agent
Hemmer, M.; Kempen, Isabelle; De Tullio, Pascal ULg et al

in Drug Development Research (2010), 71

The development of blood vessels inside tumors is required to provide the nutrients and oxygen needed for tumor growth and to allow the spread of cancer cells at a distance to form metastasis ... [more ▼]

The development of blood vessels inside tumors is required to provide the nutrients and oxygen needed for tumor growth and to allow the spread of cancer cells at a distance to form metastasis. Angiogenesis is also implicated in ocular diseases like age-related macular degeneration. The present work describes the potential anti-angiogenic properties of a coumarinic derivative, 3-bromophenyl 6-acetoxymethyl-2-oxo-2H-1-benzopyran-3-carboxylate (IK9), previously described as a potent inhibitor of HT 1080 fibrosarcoma cell invasion in vitro and tumor growth in vivo. In vivo, ex vivo, and in vitro models were used to delineate the anti-angiogenic properties of IK9. The anti-angiogenic effect of IK9 was demonstrated in vivo in a choroidal neovascularization mice model and additionally ex vivo in a rat aortic ring assay where it was more active than the known matrix metalloproteinase inhibitor Ro 28-2653. IK9 did not affect apoptosis, proliferation, or endothelial cell invasiveness in vitro. These findings suggest a complex mechanism of action of the compound via direct or indirect effects on endothelial cell properties. This study identifies IK9 as a new potent inhibitor of angiogenesis and suggests its potential use as a therapeutic agent. [less ▲]

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See detail1H NMR metabolomic approach of the laser-induced choroidal neovascularization in mice
Lambert, Vincent ULg; Frederich, Michel ULg; Rousseau, Rousseau et al

Poster (2008, August)

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See detailAngiogenesis is not impaired in connective tissue growth factor (CTGF) knock-out mice
Kuiper, Esther J.; Roestenberg, Peggy; Ehlken, Christoph et al

in Journal of Histochemistry & Cytochemistry (2007), 55(11), 1139-1147

Connective tissue growth factor (CTGF) is a member of the CCN family of growth factors. CTGF is important in scarring, wound healing, and fibrosis. It has also been implicated to play a role in ... [more ▼]

Connective tissue growth factor (CTGF) is a member of the CCN family of growth factors. CTGF is important in scarring, wound healing, and fibrosis. It has also been implicated to play a role in angiogenesis, in addition to vascular endothelial growth factor (VEGF). In the eye, angiogenesis and subsequent fibrosis are the main causes of blindness in conditions such as diabetic retinopathy. We have applied three different models of angiogenesis to homozygous CTGF(-/-) and heterozygous CTGF(+/-) mice to establish involvement of CTGF in neovascularization. CTGF(+/-) mice die around birth. Therefore, embryonic CTGF(-/-), CTGF(-/-), and CTGF(+/+) bone explants were used to study in vitro angiogenesis, and neonatal and mature CTGF(+/-) and CTGF(+/+) mice were used in models of oxygen-induced retinopathy and laser-induced choroidal neovascularization. Angiogenesis in vitro was independent of the CTGF genotype in both the presence and the absence of VEGF. Oxygen-induced vascular pathology in the retina, as determined semi-quantitatively, and laser-induced choroidal neovascularization, as determined quantitatively, were also not affected by the CTGF genotype. Our data show that downregulation of CTGF levels does not affect neovascularization, indicating distinct roles of VEGF and CTGF in angiogenesis and fibrosis in eye conditions. [less ▲]

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See detailAnti-angiogenic therapy of exudative age-related macular degeneration: current progress and emerging concepts
Noël, Agnès ULg; Jost, Maud; Lambert, Vincent ULg et al

in Trends in Molecular Medicine (2007), 13(8), 345-352

Age-related macular degeneration (AMD) is the leading cause of blindness in elderly patients. The more aggressive exudative form is characterized by abnormal blood-vessel development that occurs beneath ... [more ▼]

Age-related macular degeneration (AMD) is the leading cause of blindness in elderly patients. The more aggressive exudative form is characterized by abnormal blood-vessel development that occurs beneath the retina as a result of choroidal neovascularization (CNV). Vascular endothelial growth factor [VEGF) has emerged as the key mediator of CNV formation; this has led to intensive research on VEGF and the recent approval of anti-VEGF compounds by the US Food and Drug Administration. Despite this successful introduction of anti-angiogenic therapies into the clinical setting, there is still a lack of treatments that definitively reverse damaged vision. Here, we consider the importance of putative molecular targets other than VEGF that might have been underestimated. Emerging cellular mechanisms offer additional opportunities for innovative therapeutic approaches. [less ▲]

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See detailConnective tissue growth factor (CTGF) is not involved in angiogenesis in knock out mouse models
van Geest, R. J.; Kuiper, Esther J.; Ehlken, Christoph et al

in European Journal of Ophthalmology (2007), 17(3, MAY-JUN), 476

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See detailTumoral and choroidal vascularization: differential cellular mechanisms involving plasminogen activator inhibitor type I.
Jost, Maud; Maillard, Catherine ULg; Lecomte, Julie ULg et al

in American Journal of Pathology (2007), 171(4), 1369-80

An adequate balance between serine proteases and their plasminogen activator inhibitor-1 (PAI-1) is critical for pathological angiogenesis. PAI-1 deficiency in mice is associated with impaired choroidal ... [more ▼]

An adequate balance between serine proteases and their plasminogen activator inhibitor-1 (PAI-1) is critical for pathological angiogenesis. PAI-1 deficiency in mice is associated with impaired choroidal neovascularization (CNV) and tumoral angiogenesis. In the present work, we demonstrate unexpected differences in the contribution of bone marrow (BM)-derived cells in these two processes regulated by PAI-1. PAI-1(-/-) mice grafted with BM-derived from wild-type mice were able to support laser-induced CNV formation but not skin carcinoma vascularization. Engraftment of irradiated wild-type mice with PAI-1(-/-) BM prevented CNV formation, demonstrating the crucial role of PAI-1 delivered by BM-derived cells. In contrast, the transient infiltration of tumor transplants by local PAI-1-producing host cells rather than by BM cells was sufficient to rescue tumor growth and angiogenesis in PAI-1-deficient mice. These data identify PAI-1 as a molecular determinant of a local permissive soil for tumor angiogenesis. Altogether, the present study demonstrates that different cellular mechanisms contribute to PAI-1-regulated tumoral and CNV. PAI-1 contributes to BM-dependent choroidal vascularization and to BM-independent tumor growth and angiogenesis. [less ▲]

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See detailPlasminogen activator inhibitor type 1 (PAI-1) controls bone marrow-dependent and independent vascularization
Jost, M; Maillard, C; Lecomte, J et al

Poster (2006)

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See detailPlasminogen activator inhibitor type I (PAI-1) controls bone marrow-dependent and independent vascularization
Jost, M.; Maillard, Catherine ULg; Lambert, Vincent ULg et al

in Acta Clinica Belgica (2006), 61(2, MAR-APR), 87

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See detailRôle des protéinases et de leurs inhibiteurs dans les formes associées à une néovascularisation anormale sous-rétinienne. Caractérisation par l’étude de modèles animaux transgéniques et développements thérapeutiques.
Lambert, Vincent ULg

Doctoral thesis (2005)

La dégénérescence maculaire liée à l'âge (DMLA) est la principale cause de perte visuelle chez les personnes de plus de 70 ans dans le monde occidental. Cette cécité résulte de la perte de fonction de la ... [more ▼]

La dégénérescence maculaire liée à l'âge (DMLA) est la principale cause de perte visuelle chez les personnes de plus de 70 ans dans le monde occidental. Cette cécité résulte de la perte de fonction de la macula (au centre de la rétine) qui est responsable de la vision centrale. Cette dégénérescence réprésente un handicap social indéniable et une perte de liberté pour ces personnes atteintes, car elle affecte des activités telles que la conduite, la lecture ou tout simplement la reconnaissance d’un visage. La pathogénie de cette affection est complexe et peu comprise. La forme la plus grave de cette maladie est associée à une poussée vasculaire (angiogenèse) vers l'espace sous-rétinien qui entraîne une fibrose avec perte des photorécepteurs. La plupart des lésions ne sont pas curables par photocoagulation laser et les stratégies thérapeutiques actuelles sont insuffisantes. Nous avons étudié, dans notre laboratoire, les mécanismes moléculaires de l’angiogenèse. Ce processus invasif requiert la digestion de la matrice extracellulaire avant la prolifération et la migration des capillaires. Deux systèmes enzymatiques sont principalement impliqués dans la digestion tissulaire : le système plasminogène/plasmine et les métalloprotéinases matricielles (MMPs). 1) Le système protéolytique activateur du plasminogène/plasmine : Afin d'évaluer la pertinence biologique de ce système dans l'angiogenèse sous-rétinienne, nous avons mis au point un modèle de néovascularisation choroidienne à l'aide d'un impact laser à l'argon chez des souris déficientes pour une série de gènes fondamentaux de ce système, comparées à des souris normales. Nos observations mettent en évidence le rôle essentiel du PAI-1 dans la néovascularisation sous-rétinienne et contribuent à expliquer l'aspect multifonctionnel du PAI-1 dans l'angiogenèse. 2) Les métalloprotéinases matricielles (MMPs) : Les métalloprotéinases matricielles (MMPs) participent au remodelage normal tissulaire et sont impliquées dans un large éventail de phénomènes physiologiques et pathologiques, tels que l'invasion cellulaire tumorale, la cicatrisation et l'angiogenèse. Nous avons appliqué notre modèle expérimental à des souris déficientes pour deux types de MMP (MMP-2 et MMP-9). La déficience en MMP-2 et -9 inhibe la néovascularisation sous-rétinienne induite par laser, soulignant l’importance de cette enzyme in vivo. Ces études laissent entrevoir des perspectives thérapeutiques dans la lutte contre la DMLA par l’utilisation d’inhibiteur spécifiques des ces MMPs. En conclusion, ces différents aspects de notre étude ouvrent des perpectives de développements thérapeutiques. Ils démontrent l’importance des MMP-2, MMP-9 et de PAI-1 dans la néovascularisation sous-rétinienne. L’inhibition spécifique de ces enzymes laisse entrevoir des espoirs dans le traitement curatif de la dégénérescence maculaire liée à l’âge. Malheureusement de grandes lacunes existent encore quand aux perturbations métaboliques à l’origine de la DMLA, ce qui est l’objet de cette étude. [less ▲]

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