emilie groyer - Academia.edu (original) (raw)
Papers by emilie groyer
L'atherosclerose et sa principale complication, l'atherothrombose, sont le resultat de la... more L'atherosclerose et sa principale complication, l'atherothrombose, sont le resultat de la regulation inefficace d'une reponse inflammatoire au sein de la paroi vasculaire. Toutes les cellules impliquees dans ce processus pathologique expriment un recepteur inhibiteur, le CD31. L'objectif de mon travail de these a ete de determiner si le CD31 etait implique dans l'atherosclerose. Nous avons montre que la surexpression d'une forme soluble du CD31 permettait de prevenir le developpement de lesions dans un modele murin d'atherosclerose, les souris ApoE KO. Nous avons ensuite etabli que la survenue de l'atherothrombose, sous forme d'anevrisme ou de thrombus luminal, etait correlee au clivage du CD31 a la surface des lymphocytes T circulants. L'engagement de la portion de CD31 residuel a l'aide d'un peptide nous a permis de ralentir l'evolution de l'atherosclerose et d'empecher ses complications. En conclusion, l'ensemble de ...
Data Revues 07554982 An_00353 C2 475, Mar 27, 2008
Data Revues 07554982 An_00353 C2 475, Mar 27, 2008
Data Revues 07554982 00353 C2 475, Jan 3, 2008
Presse médicale (Paris, France : 1983), 2006
The pathogenesis of atherosclerosis remains incompletely understood. Accumulation of oxidized lip... more The pathogenesis of atherosclerosis remains incompletely understood. Accumulation of oxidized lipoproteins (oxLDL) within the vascular wall drives a related immune response very early during the disease course. Such an immune response is self-amplified and eventually escapes from physiologic control mechanisms. Certain lymphocytes may become pathogenic. B cells play a protective role by producing antibodies able to neutralize oxLDL. Elucidation of the immune control mechanisms in atherosclerosis will open the way to new therapeutic perspectives.
Atherosclerosis Supplements, 2006
Atherosclerosis Supplements, 2006
Transplantation, 2008
Lumen loss in graft arteriosclerosis is the consequence of the development of a thick neointima a... more Lumen loss in graft arteriosclerosis is the consequence of the development of a thick neointima and constrictive arterial remodeling. The latter is due to adventitial chronic inflammation and excessive perivascular collagen deposition. We reasoned that blockade of the portal of entry of inflammatory effectors may constitute a strategy to prevent constrictive arterial remodeling. We found that an anti-angiogenic therapy (ABT-510 nonapeptide), devoid of direct immunomodulatory properties, dramatically reduced adventitial angiogenesis by 66% (P<0.0001) in the rat aortic interposition model of graft arteriosclerosis. The associated decreased entry of inflammatory cells (44%; P<0.00001) resulted in drastic reduction of collagen deposition (57%; P<0.0001) thereby preventing subsequent adventitial constrictive remodeling and reduction of lumen surface area (5.26+/-0.74 vs. 8.58+/-2.48 microm2; Control vs. ABT-510-treated rats; P<0.0001). ABT-510 had no effect on the development of the neointima. This work supports the idea that targeting angiogenesis may act synergistically with conventional immunosuppressive therapy in preventing graft arteriosclerosis, a crucial feature of chronic graft rejection.
Journal of the American College of Cardiology, 2007
This study was designed to evaluate whether replacing CD31 (PECAM-1) signaling can restore the re... more This study was designed to evaluate whether replacing CD31 (PECAM-1) signaling can restore the regulation of lymphocyte activation and improve experimental atherosclerosis. Atherosclerosis, the principal cause of myocardial infarction and stroke, is due to the development of a pathogenic immune response within the vascular wall and is aggravated by the reduction of regulatory T-cells. CD31, a transmembrane adhesion molecule with inhibitory signaling functions, is physiologically expressed on blood and vascular resting cells but is lost in pathologic conditions associated with atherosclerosis. Replacement therapy with a CD31 receptor globulin (Rg) was delivered by in vivo gene transfer in 6-week-old apolipoprotein E knockout mice (n = 14 per group) every 5 weeks for 6 months. Control groups were treated with a truncated CD31Rg or with vehicle alone. At the end of the study, plaque size and morphology and blood T-cell compartment were analyzed in all mice. Atherosclerotic lesions of CD31Rg-treated mice were smaller (p < 0.01) and showed less neovascularization and intraplaque hemorrhage (p < 0.05) compared with control subjects. Furthermore, circulating regulatory T-cells were increased in vivo (p < 0.01) and showed normal suppressive function on proliferation of conventional T-cells in vitro. Indeed, CD31Rg treatment led to blunted blood T-cell activation (p < 0.05) and reduced T-cell infiltration within plaques (p < 0.01). Our data suggest that CD31 plays a key role in the regulation of the immune response linked to atherosclerosis. CD31-targeting therapeutic approaches may therefore be envisaged for preventing and treating atherosclerotic diseases.
The Journal of Immunology, 2010
Cardiovascular Research, 2012
The loss of the inhibitory receptor CD31 on peripheral T lymphocytes is associated with the incid... more The loss of the inhibitory receptor CD31 on peripheral T lymphocytes is associated with the incidence of atherosclerotic complications such as abdominal aortic aneurysms (AAA) in patients and plaque thrombosis in mice. However, we have recently discovered that a small fragment of extracellular CD31 remains expressed on the surface of the apparently 'CD31-negative' T-cells and that it is possible to restore the CD31-mediated T-cell inhibition in vivo by using a synthetic CD31-derived peptide. Here, we wanted to evaluate the therapeutic potential of the peptide in an experimental model of accelerated atherosclerosis and AAA formation.
Arteriosclerosis, Thrombosis, and Vascular Biology, 2005
Objective-The mechanism by which T cells exert a proatherogenic potential is unclear. In order to... more Objective-The mechanism by which T cells exert a proatherogenic potential is unclear. In order to determine whether this potential requires their replication, we crossed atherosclerosis-prone apolipoprotein E knockout mice (ApoE°) with transgenic mice in which exclusive and conditional ablation of dividing T cells relies on their specific expression of the herpes simplex type 1 thymidine kinase (TK) suicide gene. Methods and Results-We first showed that conalbumin-immunized ApoE°TK mice mounted a significant immune response to the antigen that was fully and specifically blocked by an in vivo ganciclovir (GCV) treatment. Next, ApoE°TK mice and ApoE°mice were treated or not with GCV either during the first 4 weeks (GCV 1 to 4w), the last 4 weeks (GCV 5 to 8w), or during 8 weeks (GCV 1 to 8w). Strikingly, ApoE°TK mice displayed a dramatic decrease in lesion development in the GCV 1 to 8w and GCV 5 to 8w groups, whereas the GCV had no effect when administered during the first 4 weeks. In protected mice, the inflammatory parameters in lesions, the percentage of CD69 ϩ CD3 ϩ splenocytes, and the circulating natural killer T cells were reduced. Conclusions-The present study, therefore, shows that the proatherogenic potential of T cells is crucial in the progression of fatty streaks to mature plaques and requires cell division. (Arterioscler Thromb Vasc Biol. 2006;26:353-358.)
Arteriosclerosis, Thrombosis, and Vascular Biology, 2005
Objective-Lymphocyte activation is thought to play a major role in the pathogenesis of atheroscle... more Objective-Lymphocyte activation is thought to play a major role in the pathogenesis of atherosclerotic complications such as plaque thrombosis. Circulating CD31 ϩ T cells have been shown to regulate human T cell activation. Aim of this study was to evaluate whether the proportion of circulating immunoregulatory CD31 ϩ T cells is correlated to the occurrence of plaque thrombosis in aged apolipoprotein (apo) E knockout (KO) mice.
Arteriosclerosis, Thrombosis, and Vascular Biology, 2005
Background-Cell-mediated immunity is considered to contribute to the pathogenesis of abdominal ao... more Background-Cell-mediated immunity is considered to contribute to the pathogenesis of abdominal aortic aneurysms (AAA). In particular, infiltrating macrophages and CD8 ϩ T lymphocytes participate in the destruction of the aortic wall extracellular matrix and smooth muscle cells. We surmise that these pathological events are controlled by circulating regulatory lymphocytes. Methods and Results-Circulating CD4 ϩ /CD31 ϩ cells were reduced in AAA patients (nϭ80, 8.9Ϯ0.6%) as compared with controls (nϭ69, 13.7Ϯ0.8%; PϽ0.001) and inversely proportional to AAA size. Exclusion of the aneurysm by an endoprothesis did not affect CD31 ϩ T cell values. Reduction of blood CD4 ϩ /CD31 ϩ cells was not attributable to their enrichment in AAA tissue. In contrast, CD8 ϩ /CD31 ϩ cells were slightly reduced in the blood while increased in the aneurysmal tissue (29.2Ϯ0.5 versus 20.2Ϯ4.7% in blood, nϭ6; PϽ0.05). Remarkably, high percentages of CD4 ϩ / CD31 ϩ cells were able to regulate proliferation and cytokine production of CD8 ϩ lymphocytes, as well as CD8 ϩ cell-mediated cytotoxicity of aortic smooth muscle cells (PϽ0.01). Finally, CD4 ϩ /CD31 ϩ cells reduced the production and activity of metalloproteinase-9 by lipopolysaccharide-stimulated macrophages.
L'atherosclerose et sa principale complication, l'atherothrombose, sont le resultat de la... more L'atherosclerose et sa principale complication, l'atherothrombose, sont le resultat de la regulation inefficace d'une reponse inflammatoire au sein de la paroi vasculaire. Toutes les cellules impliquees dans ce processus pathologique expriment un recepteur inhibiteur, le CD31. L'objectif de mon travail de these a ete de determiner si le CD31 etait implique dans l'atherosclerose. Nous avons montre que la surexpression d'une forme soluble du CD31 permettait de prevenir le developpement de lesions dans un modele murin d'atherosclerose, les souris ApoE KO. Nous avons ensuite etabli que la survenue de l'atherothrombose, sous forme d'anevrisme ou de thrombus luminal, etait correlee au clivage du CD31 a la surface des lymphocytes T circulants. L'engagement de la portion de CD31 residuel a l'aide d'un peptide nous a permis de ralentir l'evolution de l'atherosclerose et d'empecher ses complications. En conclusion, l'ensemble de ...
Data Revues 07554982 An_00353 C2 475, Mar 27, 2008
Data Revues 07554982 An_00353 C2 475, Mar 27, 2008
Data Revues 07554982 00353 C2 475, Jan 3, 2008
Presse médicale (Paris, France : 1983), 2006
The pathogenesis of atherosclerosis remains incompletely understood. Accumulation of oxidized lip... more The pathogenesis of atherosclerosis remains incompletely understood. Accumulation of oxidized lipoproteins (oxLDL) within the vascular wall drives a related immune response very early during the disease course. Such an immune response is self-amplified and eventually escapes from physiologic control mechanisms. Certain lymphocytes may become pathogenic. B cells play a protective role by producing antibodies able to neutralize oxLDL. Elucidation of the immune control mechanisms in atherosclerosis will open the way to new therapeutic perspectives.
Atherosclerosis Supplements, 2006
Atherosclerosis Supplements, 2006
Transplantation, 2008
Lumen loss in graft arteriosclerosis is the consequence of the development of a thick neointima a... more Lumen loss in graft arteriosclerosis is the consequence of the development of a thick neointima and constrictive arterial remodeling. The latter is due to adventitial chronic inflammation and excessive perivascular collagen deposition. We reasoned that blockade of the portal of entry of inflammatory effectors may constitute a strategy to prevent constrictive arterial remodeling. We found that an anti-angiogenic therapy (ABT-510 nonapeptide), devoid of direct immunomodulatory properties, dramatically reduced adventitial angiogenesis by 66% (P<0.0001) in the rat aortic interposition model of graft arteriosclerosis. The associated decreased entry of inflammatory cells (44%; P<0.00001) resulted in drastic reduction of collagen deposition (57%; P<0.0001) thereby preventing subsequent adventitial constrictive remodeling and reduction of lumen surface area (5.26+/-0.74 vs. 8.58+/-2.48 microm2; Control vs. ABT-510-treated rats; P<0.0001). ABT-510 had no effect on the development of the neointima. This work supports the idea that targeting angiogenesis may act synergistically with conventional immunosuppressive therapy in preventing graft arteriosclerosis, a crucial feature of chronic graft rejection.
Journal of the American College of Cardiology, 2007
This study was designed to evaluate whether replacing CD31 (PECAM-1) signaling can restore the re... more This study was designed to evaluate whether replacing CD31 (PECAM-1) signaling can restore the regulation of lymphocyte activation and improve experimental atherosclerosis. Atherosclerosis, the principal cause of myocardial infarction and stroke, is due to the development of a pathogenic immune response within the vascular wall and is aggravated by the reduction of regulatory T-cells. CD31, a transmembrane adhesion molecule with inhibitory signaling functions, is physiologically expressed on blood and vascular resting cells but is lost in pathologic conditions associated with atherosclerosis. Replacement therapy with a CD31 receptor globulin (Rg) was delivered by in vivo gene transfer in 6-week-old apolipoprotein E knockout mice (n = 14 per group) every 5 weeks for 6 months. Control groups were treated with a truncated CD31Rg or with vehicle alone. At the end of the study, plaque size and morphology and blood T-cell compartment were analyzed in all mice. Atherosclerotic lesions of CD31Rg-treated mice were smaller (p < 0.01) and showed less neovascularization and intraplaque hemorrhage (p < 0.05) compared with control subjects. Furthermore, circulating regulatory T-cells were increased in vivo (p < 0.01) and showed normal suppressive function on proliferation of conventional T-cells in vitro. Indeed, CD31Rg treatment led to blunted blood T-cell activation (p < 0.05) and reduced T-cell infiltration within plaques (p < 0.01). Our data suggest that CD31 plays a key role in the regulation of the immune response linked to atherosclerosis. CD31-targeting therapeutic approaches may therefore be envisaged for preventing and treating atherosclerotic diseases.
The Journal of Immunology, 2010
Cardiovascular Research, 2012
The loss of the inhibitory receptor CD31 on peripheral T lymphocytes is associated with the incid... more The loss of the inhibitory receptor CD31 on peripheral T lymphocytes is associated with the incidence of atherosclerotic complications such as abdominal aortic aneurysms (AAA) in patients and plaque thrombosis in mice. However, we have recently discovered that a small fragment of extracellular CD31 remains expressed on the surface of the apparently 'CD31-negative' T-cells and that it is possible to restore the CD31-mediated T-cell inhibition in vivo by using a synthetic CD31-derived peptide. Here, we wanted to evaluate the therapeutic potential of the peptide in an experimental model of accelerated atherosclerosis and AAA formation.
Arteriosclerosis, Thrombosis, and Vascular Biology, 2005
Objective-The mechanism by which T cells exert a proatherogenic potential is unclear. In order to... more Objective-The mechanism by which T cells exert a proatherogenic potential is unclear. In order to determine whether this potential requires their replication, we crossed atherosclerosis-prone apolipoprotein E knockout mice (ApoE°) with transgenic mice in which exclusive and conditional ablation of dividing T cells relies on their specific expression of the herpes simplex type 1 thymidine kinase (TK) suicide gene. Methods and Results-We first showed that conalbumin-immunized ApoE°TK mice mounted a significant immune response to the antigen that was fully and specifically blocked by an in vivo ganciclovir (GCV) treatment. Next, ApoE°TK mice and ApoE°mice were treated or not with GCV either during the first 4 weeks (GCV 1 to 4w), the last 4 weeks (GCV 5 to 8w), or during 8 weeks (GCV 1 to 8w). Strikingly, ApoE°TK mice displayed a dramatic decrease in lesion development in the GCV 1 to 8w and GCV 5 to 8w groups, whereas the GCV had no effect when administered during the first 4 weeks. In protected mice, the inflammatory parameters in lesions, the percentage of CD69 ϩ CD3 ϩ splenocytes, and the circulating natural killer T cells were reduced. Conclusions-The present study, therefore, shows that the proatherogenic potential of T cells is crucial in the progression of fatty streaks to mature plaques and requires cell division. (Arterioscler Thromb Vasc Biol. 2006;26:353-358.)
Arteriosclerosis, Thrombosis, and Vascular Biology, 2005
Objective-Lymphocyte activation is thought to play a major role in the pathogenesis of atheroscle... more Objective-Lymphocyte activation is thought to play a major role in the pathogenesis of atherosclerotic complications such as plaque thrombosis. Circulating CD31 ϩ T cells have been shown to regulate human T cell activation. Aim of this study was to evaluate whether the proportion of circulating immunoregulatory CD31 ϩ T cells is correlated to the occurrence of plaque thrombosis in aged apolipoprotein (apo) E knockout (KO) mice.
Arteriosclerosis, Thrombosis, and Vascular Biology, 2005
Background-Cell-mediated immunity is considered to contribute to the pathogenesis of abdominal ao... more Background-Cell-mediated immunity is considered to contribute to the pathogenesis of abdominal aortic aneurysms (AAA). In particular, infiltrating macrophages and CD8 ϩ T lymphocytes participate in the destruction of the aortic wall extracellular matrix and smooth muscle cells. We surmise that these pathological events are controlled by circulating regulatory lymphocytes. Methods and Results-Circulating CD4 ϩ /CD31 ϩ cells were reduced in AAA patients (nϭ80, 8.9Ϯ0.6%) as compared with controls (nϭ69, 13.7Ϯ0.8%; PϽ0.001) and inversely proportional to AAA size. Exclusion of the aneurysm by an endoprothesis did not affect CD31 ϩ T cell values. Reduction of blood CD4 ϩ /CD31 ϩ cells was not attributable to their enrichment in AAA tissue. In contrast, CD8 ϩ /CD31 ϩ cells were slightly reduced in the blood while increased in the aneurysmal tissue (29.2Ϯ0.5 versus 20.2Ϯ4.7% in blood, nϭ6; PϽ0.05). Remarkably, high percentages of CD4 ϩ / CD31 ϩ cells were able to regulate proliferation and cytokine production of CD8 ϩ lymphocytes, as well as CD8 ϩ cell-mediated cytotoxicity of aortic smooth muscle cells (PϽ0.01). Finally, CD4 ϩ /CD31 ϩ cells reduced the production and activity of metalloproteinase-9 by lipopolysaccharide-stimulated macrophages.