References of "Collen, Désiré"
     in
Bookmark and Share    
Full Text
Peer Reviewed
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 ▲]

Detailed reference viewed: 126 (10 ULg)
Full Text
Peer Reviewed
See detailModulation of angiogenesis during adipose tissue development in murine models of obesity.
Vörös, Gabor; Maquoi, Erik ULg; Demeulemeester, Diego et al

in Endocrinology (2005), 146(10), 4545-4554

Development of vasculature and mRNA expression of 17 pro- or antiangiogenic factors were studied during adipose tissue development in nutritionally induced or genetically determined murine obesity models ... [more ▼]

Development of vasculature and mRNA expression of 17 pro- or antiangiogenic factors were studied during adipose tissue development in nutritionally induced or genetically determined murine obesity models. Subcutaneous (SC) and gonadal (GON) fat pads were harvested from male C57Bl/6 mice kept on standard chow [standard fat diet (SFD)] or on high-fat diet for 0-15 wk and from male ob/ob mice kept on SFD. Ob/ob mice and C57Bl/6 mice on high-fat diet had significantly larger SC and GON fat pads, accompanied by significantly higher blood content, increased total blood vessel volume, and higher number of proliferating cells. mRNA and protein levels of angiopoietin (Ang)-1 were down-regulated, whereas those of thrombospondin-1 were up-regulated in developing adipose tissue in both obesity models. Ang-1 mRNA levels correlated negatively with adipose tissue weight in the early phase of nutritionally induced obesity as well as in genetically determined obesity. Placental growth factor and Ang-2 expression were increased in SC adipose tissue of ob/ob mice, and thrombospondin-2 was increased in both their SC and GON fat pads. mRNA levels of vascular endothelial growth factor (VEGF)-A isoforms VEGF-B, VEGF-C, VEGF receptor-1, -2, and -3, and neuropilin-1 were not markedly modulated by obesity. This modulation of angiogenic factors during development of adipose tissue supports their important functional role in obesity. [less ▲]

Detailed reference viewed: 15 (2 ULg)
Full Text
Peer Reviewed
See detailRole of Gas-6 in adipogenesis and nutritionally induced adipose tissue development in mice.
Maquoi, Erik ULg; Vörös, Gabor; Carmeliet, Peter et al

in Arteriosclerosis, Thrombosis, and Vascular Biology (2005), 25(5), 1002-1007

OBJECTIVE: A potential role of growth arrest-specific gene 6 (Gas-6) in energy storage in adipose tissue was investigated in murine models of obesity. Gas-6 is a ligand for the Axl, C-Mer, and Sky family ... [more ▼]

OBJECTIVE: A potential role of growth arrest-specific gene 6 (Gas-6) in energy storage in adipose tissue was investigated in murine models of obesity. Gas-6 is a ligand for the Axl, C-Mer, and Sky family of tyrosine kinase receptors. METHODS AND RESULTS: Whereas Gas-6, C-Mer, and Sky were expressed in mature murine adipocytes, the expression of Axl was restricted to the stromal-vascular fraction, which includes pre-adipocytes. During the in vitro conversion of adipogenic 3T3-F442A cells into mature adipocytes, the expression of Gas-6 increased in undifferentiated confluent pre-adipocytes during a transient phase of growth arrest. On treatment of these cells with an adipogenic medium, Gas-6 expression decreased sharply, coinciding with expression of early adipocytes markers. This modulation was not observed in the nonadipogenic 3T3-C2 cells. The Gas-6 mRNA level was transiently downregulated during nutritionally induced expansion of adipose tissues in vivo. When kept on a standard diet, no significant difference in either total body weight or weight of gonadal or subcutaneous fat pads was observed between Gas-6 deficient and wild-type mice. On exposure to a high-fat diet, however, Gas-6-deficient mice had significantly less fat mass than their wild-type counterparts. CONCLUSIONS: Gas-6 enhances the accumulation of adipose tissue in diet-induced obese mice. [less ▲]

Detailed reference viewed: 16 (1 ULg)
Full Text
Peer Reviewed
See detailInfluence of membrane-bound tumor necrosis factor (TNF)-alpha on obesity and glucose metabolism
Vörös, Gabor; Maquoi, Erik ULg; Collen, Désiré et al

in Journal of Thrombosis and Haemostasis [=JTH] (2004), 2(3), 507-513

OBJECTIVES: To investigate the influence of transmembrane tumor necrosis factor (TNF)-alpha on adipose tissue development and insulin-mediated glucose metabolism. METHODS AND RESULTS: TNF-alpha and ... [more ▼]

OBJECTIVES: To investigate the influence of transmembrane tumor necrosis factor (TNF)-alpha on adipose tissue development and insulin-mediated glucose metabolism. METHODS AND RESULTS: TNF-alpha and lymphotoxin-alpha-deficient mice expressing non-cleavable transmembrane TNF-alpha (Tg-tmTNF-alpha) and TNF-alpha/lymphotoxin-alpha double knockout (control) mice were kept on high-fat diet for 15 weeks. The food intake and feeding efficiency of Tg-tmTNF-alpha mice were significantly higher compared with control mice. At the end of the study, Tg-tmTNF-alpha mice had a significantly higher total body weight, as well as subcutaneous and gonadal adipose tissue mass. Histological analysis revealed that the expression of Tg-tmTNF-alpha resulted in a significantly increased adipocyte area and blood vessel density. Plasma leptin levels correlated positively with adipose tissue mass. The plasma levels of total cholesterol and HDL-cholesterol were significantly increased and LDL-cholesterol levels significantly decreased in Tg-tmTNF-alpha mice. Fasting blood glucose and plasma insulin levels were not different between the two genotypes and intraperitoneal glucose and insulin tolerance tests did not show significant differences. CONCLUSIONS: Transmembrane TNF-alpha enhances adipose tissue formation without altering insulin-mediated glucose metabolism in mice with nutritionally induced obesity. [less ▲]

Detailed reference viewed: 37 (1 ULg)
Full Text
Peer Reviewed
See detailEnhanced nutritionally induced adipose tissue development in mice with stromelysin-1 gene inactivation.
Maquoi, Erik ULg; Demeulemeester, Diego; Vörös, Gabor et al

in Thrombosis and Haemostasis (2003), 89(4), 696-704

To investigate a potential role of stromelysin-1 (MMP-3) in development of adipose tissue, 5 week old male MMP-3 deficient mice (MMP-3(-/-)) and wild-type (MMP-3(+/+)) controls were kept on a high fat ... [more ▼]

To investigate a potential role of stromelysin-1 (MMP-3) in development of adipose tissue, 5 week old male MMP-3 deficient mice (MMP-3(-/-)) and wild-type (MMP-3(+/+)) controls were kept on a high fat diet (HFD) for 15 weeks. MMP-3(-/-) mice were hyperphagic and gained more weight than the MMP-3(+/+) mice. At the time of sacrifice, the body weight of the MMP-3(-/-) mice was significantly higher than that of the MMP-3(+/+) mice, as was the weight of the isolated subcutaneous (SC) and gonadal (GON) fat deposits. Significant adipocyte hypertrophy was observed in the GON but not in the SC adipose tissue of MMP-3(-/-) mice. Fasting plasma glucose and cholesterol levels were comparable in both genotypes, whereas triglyceride levels were significantly lower in MMP-3(-/-) mice. Staining with an endothelial cell specific lectin revealed a significantly higher blood vessel density and larger total stained area in the GON adipose tissues of MMP-3(-/-) mice. Thus, in a murine model of nutritionally induced obesity, MMP-3 impairs adipose tissue development, possibly by affecting food intake and/or adipose tissue-related angiogenesis. [less ▲]

Detailed reference viewed: 27 (2 ULg)
Full Text
Peer Reviewed
See detailDeficiency of tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) impairs nutritionally induced obesity in mice.
Lijnen, Roger; Demeulemeester, Diego; Van Hoef, B. et al

in Thrombosis and Haemostasis (2003), 89(2), 249-255

Tissue inhibitor of matrix metalloproteinase-1 deficient (TIMP-1(-/-)) mice and wild-type (TIMP-1(+/+)) controls were kept on a standard (SFD) or a high fat diet (HFD) for 15 weeks. At the time of ... [more ▼]

Tissue inhibitor of matrix metalloproteinase-1 deficient (TIMP-1(-/-)) mice and wild-type (TIMP-1(+/+)) controls were kept on a standard (SFD) or a high fat diet (HFD) for 15 weeks. At the time of sacrifice, TIMP-1(-/-) mice on HFD had a significantly lower body weight (29 +/- 1.5 versus 41 +/- 1.8 g, p <0.005), and significantly less subcutaneous (0.81 +/- 0.19 versus 1.78 +/- 0.21 g, p <0.05) and gonadal (0.87 +/- 0.17 versus 1.85 +/- 0.18 g, p <0.005) fat mass. These differences were much less pronounced for mice on SFD. On HFD but not on SFD, adipocyte diameters were significantly lower in the adipose tissue of TIMP-1(-/-) mice. Plasma leptin levels in TIMP-1(-/-) mice on HFD were significantly lower as compared to TIMP-1(+/-) mice, and strongly correlated with adipose tissue mass for both genotypes. Staining with an endothelial cell specific lectin revealed a significantly higher blood vessel density, larger stained area and vessel size in adipose tissue of TIMP-1(-/-) mice on HFD. This difference disappeared after normalization to the adipocyte number, suggesting that it does not represent a true enhancement of angiogenesis. Thus, in a murine model of nutritionally induced obesity, TIMP-1 promotes adipose tissue development. [less ▲]

Detailed reference viewed: 42 (0 ULg)
Full Text
Peer Reviewed
See detailDifferential expression of plasminogen activator inhibitor-1, tumor necrosis factor-alpha, TNF-alpha converting enzyme and ADAMTS family members in murine fat territories
Vörös, Gabor; Maquoi, Erik ULg; Collen, Désiré et al

in Biochimica et Biophysica Acta-Gene Structure and Expression (2003), 1625(1), 36-42

ur objective was to investigate expression of A disintegrin and metalloproteinase (ADAM) and ADAM proteins with a thrombospondin (TS) motif (ADAMTS) family members in adipose tissue of lean and obese mice ... [more ▼]

ur objective was to investigate expression of A disintegrin and metalloproteinase (ADAM) and ADAM proteins with a thrombospondin (TS) motif (ADAMTS) family members in adipose tissue of lean and obese mice. Five-week-old male mice were kept on standard chow (SFD) or on high fat diet (HFD) for 15 weeks, and subcutaneous (SC) and gonadal (GON) adipose tissue, as well as mature adipocytes and stromal–vascular (S–V) cells were harvested. mRNA levels of plasminogen activator inhibitor-1 (PAI-1), tumor necrosis factor-α (TNF-α), ADAM-17 (TACE or TNF-α converting enzyme), ADAMTS-1 and ADAMTS-8 were quantified in isolated adipose tissues and cell fractions, and during differentiation of murine preadipocytes. The HFD resulted in a significantly enhanced weight of isolated SC and GON fat pads, and in enhanced blood levels of glucose, cholesterol and PAI-1. ADAM-17, TNF-α, PAI-1, ADAMTS-1 and ADAMTS-8 mRNA were detected in both SC and GON adipose tissue of lean mice (SFD). In SC adipose tissue of obese mice (HFD), the expression of ADAM-17 and PAI-1 was enhanced and that of ADAMTS-1 reduced, whereas in GON adipose tissue expression of TNF-α was enhanced and that of ADAMTS-8 reduced. In lean and obese mice, expression of ADAM-17, ADAMTS-1 and ADAMTS-8 was higher in the S–V cell fraction than in mature adipocytes. During differentiation of murine 3T3-F442A preadipocytes, expression of ADAM-17 and ADAMTS-1 remained virtually unaltered, whereas that of ADAMTS-8 decreased as adipocytes matured. Several ADAM and ADAMTS family members are expressed in adipose tissue and during differentiation of preadipocytes. Modulation of their expression upon development of obesity is adipose tissue-dependent. [less ▲]

Detailed reference viewed: 10 (0 ULg)
Full Text
Peer Reviewed
See detailNutritionally induced obesity is attenuated in transgenic mice overexpressing plasminogen activator inhibitor-1
Lijnen, Roger; Maquoi, Erik ULg; Morange, Pierre et al

in Arteriosclerosis, Thrombosis, and Vascular Biology (2003), 23(1), 78-84

OBJECTIVE: The objective of this study was to investigate the role of plasminogen activator inhibitor-1 (PAI-1) in adipose tissue development in vivo. METHODS AND RESULTS: Transgenic (Tg) mice ... [more ▼]

OBJECTIVE: The objective of this study was to investigate the role of plasminogen activator inhibitor-1 (PAI-1) in adipose tissue development in vivo. METHODS AND RESULTS: Transgenic (Tg) mice overexpressing murine PAI-1 under control of the adipocyte promoter aP2 and wild-type (WT) controls were kept on standard food (SFD) or on high-fat diet (HFD) for 15 weeks. The body weight and the weight of the isolated subcutaneous and gonadal fat deposits of the Tg mice kept on the HFD were significantly lower than those of the WT mice. The number of adipocytes in the adipose tissue was similar for Tg and WT mice on the HFD, but adipocyte hypotrophy and a significantly lower ratio of stroma cells/adipocytes were observed in the Tg mice. A significant negative correlation (P<0.01) was observed between expression of preadipocyte factor-1, which blocks adipocyte differentiation, and adipose tissue weight. Fasting insulin and total cholesterol levels on the HFD were lower in Tg than in WT mice. CONCLUSIONS: High circulating PAI-1 levels attenuate nutritionally induced obesity. This may be related to modifications in adipose tissue cellularity affecting weight and plasma metabolic parameters. [less ▲]

Detailed reference viewed: 11 (1 ULg)
Full Text
Peer Reviewed
See detailModulation of fibrinolytic and gelatinolytic activity during adipose tissue development in a mouse model of nutritionally induced obesity
Lijnen, Roger; Maquoi, Erik ULg; Demeulemeester, Désiré et al

in Thrombosis and Haemostasis (2002), 88(2), 345-353

A nutritionally induced obesity model was used to investigate the modulation of fibrinolytic and gelatinolytic activity during the development of adipose tissue. Five week old male mice were fed a ... [more ▼]

A nutritionally induced obesity model was used to investigate the modulation of fibrinolytic and gelatinolytic activity during the development of adipose tissue. Five week old male mice were fed a standard fat diet (SFD, 13% kcal as fat) or a high fat diet (HFD, 42% kcal as fat) for up to 15 weeks. The HFD resulted in body weights of 31 +/- 0.9 g, 38 +/- 2.0 g and 47 +/- 1.9 g at 5, 10 and 15 weeks, respectively; corresponding values for mice on the SFD were 26 +/- 0.6 g, 31 +/- 0.9 g and 31 +/- 1.2 g (all p < 0.001). The weight of the isolated subcutaneous (s.c.) or gonadal (GON) fat after 15 weeks of HFD was 1,870 +/- 180 mg or 1,470 +/- 160 mg, as compared to 250 +/- 58 mg or 350 +/- 71 mg for the SFD (p < 0.001). The HFD induced marked time-dependent hyperglycemia and elevated levels of triglycerides and total cholesterol. The HFD diet also induced a marked hypertrophy of the adipocytes as compared to the SFD, e.g. diameter of 83 +/- 3.0 microns versus 52 +/- 4.2 microns for GON adipocytes at 15 weeks (p < 0.005). Plasma plasminogen activator inhibitor-1 (PAI-1) levels were higher in mice on the HFD as compared to the SFD; they were comparable in extracts of s.c. or GON adipose tissue, whereas at different time points tissue-type (t-PA) and urokinase-type (u-PA) plasminogen activator activity was somewhat lower in the adipose tissues of mice on HFD. Gelatinolytic activity (mainly MMP-2) was detected in s.c. but not in GON adipose tissue of mice on SFD, and decreased on the HFD. In situ zymography on cryosections did not reveal different fibrinolytic activities in s.c. or GON adipose tissues of the HFD as compared to the SFD groups, whereas significantly lower gelatinolytic and higher caseinolytic activities were detected in s.c. and GON tissues of mice on the HFD (p < or = 0.05). The fibrillar collagen content was lower in adipose tissue of mice on HFD. Thus, in this model time-dependent development of adipose tissue appears to be associated with modulation of proteolytic activity. [less ▲]

Detailed reference viewed: 17 (2 ULg)
Full Text
Peer Reviewed
See detailModulation of adipose tissue expression of murine matrix metalloproteinases and their tissue inhibitors with obesity
Maquoi, Erik ULg; Munaut, Carine ULg; Colige, Alain ULg et al

in Diabetes (2002), 51(4), 1093-1101

The potential role of the matrix metalloproteinase (MMP) system in the pathophysiology of the adipose tissue was investigated in a mouse model of nutritionally induced obesity. mRNA levels of 16 MMPs and ... [more ▼]

The potential role of the matrix metalloproteinase (MMP) system in the pathophysiology of the adipose tissue was investigated in a mouse model of nutritionally induced obesity. mRNA levels of 16 MMPs and 4 tissue inhibitors of MMPs (TIMPs) were measured by semiquantitative RT-PCR in adipose tissue isolated from mice maintained for 15 weeks on a standard or high-fat diet. In mice on standard diet, with the exception of MMP-8, all MMP and TIMP transcripts were detected in both gonadal and subcutaneous depots. In obese mice, the expression of MMP-3, -11, -12, -13, and -14 and TIMP-1 mRNAs was upregulated, whereas that of MMP-7, -9, -16, and -24 and TIMP-4 was downregulated. Most MMP and TIMP mRNAs were expressed at higher levels in stromal-vascular cells than in mature adipocytes. Analysis of adipose tissue by in situ fluorescent zymography revealed MMP-dependent proteolytic activities, demonstrating the presence of active MMPs in the intact tissue. In vitro conversion of adipogenic 3T3-F442A cells into mature adipocytes was associated with substantial modulations of MMP and TIMP expression. Moreover, this in vitro adipogenesis was reduced in the presence of a synthetic MMP inhibitor. Thus, the adipose tissue expresses a large array of MMPs and TIMPs, which modulate adipocyte differentiation. [less ▲]

Detailed reference viewed: 12 (1 ULg)
Full Text
Peer Reviewed
See detailMatrix metalloproteinase inhibition impairs adipose tissue development in mice
Lijnen, Roger; Maquoi, Erik ULg; Hansen, L. B. et al

in Arteriosclerosis, Thrombosis, and Vascular Biology (2002), 22(3), 374-379

The effect of galardin, a broad-spectrum matrix metalloproteinase (MMP) inhibitor, was studied in mice kept on a high fat diet (HFD). Five-week-old male wild-type mice were fed the HFD (42% fat) for up to ... [more ▼]

The effect of galardin, a broad-spectrum matrix metalloproteinase (MMP) inhibitor, was studied in mice kept on a high fat diet (HFD). Five-week-old male wild-type mice were fed the HFD (42% fat) for up to 12 weeks and were daily injected intraperitoneally with the inhibitor (100 mg/kg) or with vehicle. After 12 weeks of the HFD, the body weights of both groups were comparable, but the weight of the isolated subcutaneous (SC) or gonadal (GON) fat deposits was significantly lower in the inhibitor-treated group than in the control group (88 +/- 11 versus 251 +/- 66 mg, respectively, for SC fat [P<0.05]; 90 +/- 24 versus 217 +/- 30 mg, respectively, for GON fat [P<0.02]). The number of adipocytes was somewhat higher and the diameter was somewhat smaller (but not significantly) in adipose tissues of the inhibitor-treated group. Adipose tissue of the inhibitor-treated mice contained more collagen than did that of the vehicle-treated mice (Sirius red-stained area of 42 +/- 2.6% versus 22 +/- 4.4%, respectively, for SC fat [P<0.05]; 21 +/- 5.1% versus 4.7 +/- 0.92%, respectively, for GON fat [P<0.01]); a distinct collagen-rich cap was formed around the inhibitor-treated tissue. In situ zymography with casein- or gelatin-containing gels confirmed a reduced MMP activity in SC and GON adipose tissues of inhibitor-treated mice. Thus, in this model, growth and development of adipose tissue appears to be limited by the formation of a collagen-rich matrix cap around the inhibitor-treated tissue. These data suggest a functional role for MMPs in the development of adipose tissue. [less ▲]

Detailed reference viewed: 4 (0 ULg)
Full Text
Peer Reviewed
See detailSynergism between vascular endothelial growth factor and placental growth factor contributes to angiogenesis and plasma extravasation in pathological conditions
Carmeliet, Peter; Moons, Lieve; Luttun, Aernout et al

in Nature Medicine (2001), 7(5), 575-583

Vascular endothelial growth factor (VEGF) stimulates angiogenesis by activating VEGF receptor-2 (VEGFR-2). The role of its homolog, placental growth factor (PlGF), remains unknown. Both VEGF and PlGF bind ... [more ▼]

Vascular endothelial growth factor (VEGF) stimulates angiogenesis by activating VEGF receptor-2 (VEGFR-2). The role of its homolog, placental growth factor (PlGF), remains unknown. Both VEGF and PlGF bind to VEGF receptor-1 (VEGFR-1), but it is unknown whether VEGFR-1, which exists as a soluble or a membrane-bound type, is an inert decoy or a signaling receptor for PlGF during angiogenesis. Here, we report that embryonic angiogenesis in mice was not affected by deficiency of PlGF (Pgf -/-). VEGF-B, another ligand of VEGFR-1, did not rescue development in Pgf -/- mice. However, loss of PlGF impaired angiogenesis, plasma extravasation and collateral growth during ischemia, inflammation, wound healing and cancer. Transplantation of wild-type bone marrow rescued the impaired angiogenesis and collateral growth in Pgf -/- mice, indicating that PlGF might have contributed to vessel growth in the adult by mobilizing bone-marrow−derived cells. The synergism between PlGF and VEGF was specific, as PlGF deficiency impaired the response to VEGF, but not to bFGF or histamine. VEGFR-1 was activated by PlGF, given that anti-VEGFR-1 antibodies and a Src-kinase inhibitor blocked the endothelial response to PlGF or VEGF/PlGF. By upregulating PlGF and the signaling subtype of VEGFR-1, endothelial cells amplify their responsiveness to VEGF during the 'angiogenic switch' in many pathological disorders. [less ▲]

Detailed reference viewed: 392 (10 ULg)