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Tu-P10:425 Anti-beta2-glycoprotein I antibodies do not increase in acute coronary syndromes
278
Tues&ty, June 20, 2006: Poster Session PIO Biomarkers for cardiovascular disectse
In conclusion, helicobacter pylori seems to be followed by dyslipidemia and endothelium inflammation, so it must be one more risk factor for atherosderosis.
I Tu-P10:425 I ANTI-BETA2-GLYCOPROTEIN I ANTIBODIES DO NOT I N C R E A S E IN A C U T E C O R O N A R Y SYNDROMES A.M.B. Medeiros 1, C.A. Von Mulhen 1 , L.C. Bodanese 1 , G. Norman 2.
1Faculdade de Medicina Pucrs, Porto Alegre, Brazil." 21nova Lab Inc, San Diego, USA B a c k g r o u n d : The role of the humoral immune response in atherogenesis remains unclear. The beta2-glycoprotein I (beta2-gpI) phospholipid cofactor is a natural anticoagulant and was found in atherosclerotic plaques. Anti-beta2-gpI antibodies were found in the immunoassays of patients with thromboembolic pulmonary hypertension, cerebral infarction and coronary artery disease (CAD). Acute coronary syndromes (ACS) reflect coronary plaques instability and antibodies against beta2-gpI might play a role in its pathogenesis. Objective: To test the hypothesis that higher levels of anti-beta2-gpI axe found in patients with ACS compared to those found in patients with chronic CAD. M e t h o d s : Case-control study of incident cases. Antibodies against beta2gpI titers (IgA, IgG and IgM) were measured by ELISA (INOVA Diagnostics, Inc., San Diego,USA) in 90 patients with ACS, defined by clinical presentation, electrocardiogram and biochemical markers of myocardial damage (cases) and 90 patients with chronic CAD, (controls), defined by a prior myocaxdial infaxction or a prior myocardial revasculaxization procedure. Sample size was calculated a priori. Differences between groups were determined by parametric tests, significant at a p value less than 0.05. Results: The two study groups were similar regarding age, gender, smoking status, familial history of CAD, cholesterol and triglycerides levels, statins current use. No significant difference was shown in IgA, IgG or IgM anti-beta2-gpI titers between cases and controls. Conclusion: Anti-beta2 gpI antibodies might not be a serum marker of plaque instability.
Tu-Pl 0 : 4 2 7
C O M P L E M E N T C6 D E F I C I E N C Y P R O T E C T S AGAINST DIABETES-INDUCED VASCULAR D A M A G E IN RATS
R. Candido 1 , F. Flschettl-, F. Tedesco , B. Toffoli 2, E Durigutto 3 , E. Manca 1 , M. Fonda 4, L. Cattin 4 , R. Carretta 2 , B. Fabris 2. 1Diabetic
Centre, A.S.S. 1 Triestina, Trieste, Italy: 2Department of Clinical Medicine and Neurology, Universi~ of Trieste, Trieste, Italy: 3Department of Physiology arm Pathology, Universi~ of Trieste, Trieste, Italy: 4S.C. III Medica, A.U.O. Triestina, Trieste, Italy Objectives: The mechanisms by which diabetes promotes vessel disease have not been fully delineated. The aim of this study was to determine whether complement activation may contribute to vascular disease in short-term diabetes. M e t h o d s : We used intravital videomicroscopy analysis of mesentery microvessels in four groups of PVG rats (n = 8) which were studied for 2 weeks: 1. Control PVG wild-type rats (C6+), 2. Control PVG C6-deficient rats (C6-), 3. Streptozotocin-induced diabetic PVG wild-type rats (DC6+) and 4. Diabetic PVG C6-deficient rats (DC6-). Following intravascular cell fluorescent labelling with Acridin Orange, in vivo leukocyte trafficking at post-capillaxy venules was assessed, both in the absence or in the presence of an inflammatory stimuli (thrombin 0.125 U/ml). Results: Diabetes in C6+ rats was associated with an increased vascular adhesion of leukocytes at basal conditions compared to the C6- animals. After exposure to thrombin, a significant increase of both transitory (58-4-10 vs 38-4-12 cells/200 I~m; p<0.01) and stable (22-4-8 vs 8-4-3 cells/2001~m; p<0.01) leukocyte adhesion was observed in DC6+ group compared to DC6rats. In addition, leukocyte extravasation was significantly higher in DC6+ rats compared to DC6- animals (12-4-3 vs 6-4-3 cells/400 i~m2; p<0.05). Diabetes per se was responsible for a significant increase of leukocyte trafficking. Conclusion: The activation of terminal complement complex might be of relevance in the development of early inflammatory diabetic vascular disease, thus suggesting a potential new therapeutic target for the prevention of diabetes-induced atherosclerosis.
I Tu-P10:428 I I M P A I R E D I i
I Tu-P 10:426 I T C E L L V A C C I N A T I O N M O D U L A T E S I EXPERIMENTAL ATHEROGENESIS A. Vaxthaman, J. Khallou-Laschet, E. Groyer, A.T. Gaston, S. Kaveri, G. Caligiuri, A. Nicoletti. Umrs 681, htserm-Universite Pierre et Marie Curie
(Paris 6), Paris, France Objective: T-cell activation contributes to atherogenesis. Clonal analysis of the T-cell infiltrate in lesions of ApoE mice showed an oligotypic prevalence of Vb6 TCR+CD4+ T-cells and absence of Vb7+ T cells. We studied the role of the Vb6+ T cells in lesion formation using the T-cell vaccination (TCV) procedure by injecting an inactivated CD4+ T-cell clone to elicit Vb-specific Qa- 1-restricted CDS+ regulatory T-cells. M e t h o d s : Vb6+ or Vb7+ (Ctd) CD4+ T-cell hybridomas were stimulated with conA, irradiated and intravenously injected in 6-week old ApoE female mice (n=14). 2 months later, CDS+ T-cells from lymphoid organs were tested for their cytotoxicity agadnst the 2 hybridomas. Lesions in the aortic root were analyzed on oil red O-stained slides. Results: CDS+ T-cells from the immunized mice were found to lyse specifically the hybridomas against which they were immunized. The blockade of the Vb6+ clonal expansion in these mice resulted in a significant increase in lesion density (29% reduction, p < 0.05). Conclusions: The TCV is a new strategy to control the activation of T-cell clones specific to atherosclerotic lesions. The blockade of the expansion of the CD4+Vb6+ population led to an increase in lesion density indicating an atheroprotective and possible immunomodulatory role of the prevalent CD4+ T cell population in the early stages of lesion formation in ApoE mice. Funding: This study was supported by INSERM, UPMC Paris 6 and "Fondation de France'.
C O R T I S O L R E S P O N S E IN P A T I E N T S WITH CORONARY ARTERY DISEASE - RELATION TO INFLAMMATORY ACTIVITY
J. Nilm 1'2, A.G. Olsson 2, L. Jonasson 2. 1Research Center of Cardiovascular Disease, Division of Medicine, HOgland Hospital, Eksj5, Sweden." 2Dpt of Medicbte attcl Care, Facul~ of Health Sciences, LbtkOping Universi~, LbzkOping, Sweden Objective: A defective hypothalamic-pituitaxy adrenal (HPA) axis may lead to enhanced susceptibility to inflammatory disease. The aim of this study was to study the HPA axis activity in patients with coronary artery disease (CAD) and relate the findings to systemic inflammatory activity. M e t h o d : Thirty patients with CAD and 30 healthy controls were included. Salivary cortisol was repeatedly measured during 3 days and 24-hour urinary cortisol was collected. All subjects were subjected to physical and psychological stress tests. Salivary cortisol was measured before and 30 minutes after the tests. C-reactive protein (CRP) and intedeukin(IL)-6 were measured in serum. Result: The 24-hour urinary cortisol secretion was significantly higher in patients. The morning cortisol was similar in patients and controls while the evening cortisol was significantly higher in patients. I1-6 was correlated to evening cortisol (p< 0.01). The increase in cortisol was significantly larger in controls compared to patients after both physical and psycological stress tests (p< 0.01).The basline CRP did not differ between the 2 groups but increased significantly in patients 24 hours after the stress tests. Conclusion: CAD patients showed a defective HPA response, as evidenced by hypercortisolism, a flattened diurnal slope and a blunted cortisol response to acute stressors. The dysregulated cortisol pattern was associated with systemic inflammatory activity. A malfunction of neuroendocrine-immune mechanisms may contribute to the maintenance of inflammatory activity in CAD. Funding: This work was supported by grants from the Heaxt-Lung Foundation.
XIV bztenmtional Symposium on Atheroscletosis, Rome, Italy, June 18-22, 2006
Tues&ty, June 20, 2006: Poster Session PIO Biomarkers for cardiovascular disectse
In conclusion, helicobacter pylori seems to be followed by dyslipidemia and endothelium inflammation, so it must be one more risk factor for atherosderosis.
I Tu-P10:425 I ANTI-BETA2-GLYCOPROTEIN I ANTIBODIES DO NOT I N C R E A S E IN A C U T E C O R O N A R Y SYNDROMES A.M.B. Medeiros 1, C.A. Von Mulhen 1 , L.C. Bodanese 1 , G. Norman 2.
1Faculdade de Medicina Pucrs, Porto Alegre, Brazil." 21nova Lab Inc, San Diego, USA B a c k g r o u n d : The role of the humoral immune response in atherogenesis remains unclear. The beta2-glycoprotein I (beta2-gpI) phospholipid cofactor is a natural anticoagulant and was found in atherosclerotic plaques. Anti-beta2-gpI antibodies were found in the immunoassays of patients with thromboembolic pulmonary hypertension, cerebral infarction and coronary artery disease (CAD). Acute coronary syndromes (ACS) reflect coronary plaques instability and antibodies against beta2-gpI might play a role in its pathogenesis. Objective: To test the hypothesis that higher levels of anti-beta2-gpI axe found in patients with ACS compared to those found in patients with chronic CAD. M e t h o d s : Case-control study of incident cases. Antibodies against beta2gpI titers (IgA, IgG and IgM) were measured by ELISA (INOVA Diagnostics, Inc., San Diego,USA) in 90 patients with ACS, defined by clinical presentation, electrocardiogram and biochemical markers of myocardial damage (cases) and 90 patients with chronic CAD, (controls), defined by a prior myocaxdial infaxction or a prior myocardial revasculaxization procedure. Sample size was calculated a priori. Differences between groups were determined by parametric tests, significant at a p value less than 0.05. Results: The two study groups were similar regarding age, gender, smoking status, familial history of CAD, cholesterol and triglycerides levels, statins current use. No significant difference was shown in IgA, IgG or IgM anti-beta2-gpI titers between cases and controls. Conclusion: Anti-beta2 gpI antibodies might not be a serum marker of plaque instability.
Tu-Pl 0 : 4 2 7
C O M P L E M E N T C6 D E F I C I E N C Y P R O T E C T S AGAINST DIABETES-INDUCED VASCULAR D A M A G E IN RATS
R. Candido 1 , F. Flschettl-, F. Tedesco , B. Toffoli 2, E Durigutto 3 , E. Manca 1 , M. Fonda 4, L. Cattin 4 , R. Carretta 2 , B. Fabris 2. 1Diabetic
Centre, A.S.S. 1 Triestina, Trieste, Italy: 2Department of Clinical Medicine and Neurology, Universi~ of Trieste, Trieste, Italy: 3Department of Physiology arm Pathology, Universi~ of Trieste, Trieste, Italy: 4S.C. III Medica, A.U.O. Triestina, Trieste, Italy Objectives: The mechanisms by which diabetes promotes vessel disease have not been fully delineated. The aim of this study was to determine whether complement activation may contribute to vascular disease in short-term diabetes. M e t h o d s : We used intravital videomicroscopy analysis of mesentery microvessels in four groups of PVG rats (n = 8) which were studied for 2 weeks: 1. Control PVG wild-type rats (C6+), 2. Control PVG C6-deficient rats (C6-), 3. Streptozotocin-induced diabetic PVG wild-type rats (DC6+) and 4. Diabetic PVG C6-deficient rats (DC6-). Following intravascular cell fluorescent labelling with Acridin Orange, in vivo leukocyte trafficking at post-capillaxy venules was assessed, both in the absence or in the presence of an inflammatory stimuli (thrombin 0.125 U/ml). Results: Diabetes in C6+ rats was associated with an increased vascular adhesion of leukocytes at basal conditions compared to the C6- animals. After exposure to thrombin, a significant increase of both transitory (58-4-10 vs 38-4-12 cells/200 I~m; p<0.01) and stable (22-4-8 vs 8-4-3 cells/2001~m; p<0.01) leukocyte adhesion was observed in DC6+ group compared to DC6rats. In addition, leukocyte extravasation was significantly higher in DC6+ rats compared to DC6- animals (12-4-3 vs 6-4-3 cells/400 i~m2; p<0.05). Diabetes per se was responsible for a significant increase of leukocyte trafficking. Conclusion: The activation of terminal complement complex might be of relevance in the development of early inflammatory diabetic vascular disease, thus suggesting a potential new therapeutic target for the prevention of diabetes-induced atherosclerosis.
I Tu-P10:428 I I M P A I R E D I i
I Tu-P 10:426 I T C E L L V A C C I N A T I O N M O D U L A T E S I EXPERIMENTAL ATHEROGENESIS A. Vaxthaman, J. Khallou-Laschet, E. Groyer, A.T. Gaston, S. Kaveri, G. Caligiuri, A. Nicoletti. Umrs 681, htserm-Universite Pierre et Marie Curie
(Paris 6), Paris, France Objective: T-cell activation contributes to atherogenesis. Clonal analysis of the T-cell infiltrate in lesions of ApoE mice showed an oligotypic prevalence of Vb6 TCR+CD4+ T-cells and absence of Vb7+ T cells. We studied the role of the Vb6+ T cells in lesion formation using the T-cell vaccination (TCV) procedure by injecting an inactivated CD4+ T-cell clone to elicit Vb-specific Qa- 1-restricted CDS+ regulatory T-cells. M e t h o d s : Vb6+ or Vb7+ (Ctd) CD4+ T-cell hybridomas were stimulated with conA, irradiated and intravenously injected in 6-week old ApoE female mice (n=14). 2 months later, CDS+ T-cells from lymphoid organs were tested for their cytotoxicity agadnst the 2 hybridomas. Lesions in the aortic root were analyzed on oil red O-stained slides. Results: CDS+ T-cells from the immunized mice were found to lyse specifically the hybridomas against which they were immunized. The blockade of the Vb6+ clonal expansion in these mice resulted in a significant increase in lesion density (29% reduction, p < 0.05). Conclusions: The TCV is a new strategy to control the activation of T-cell clones specific to atherosclerotic lesions. The blockade of the expansion of the CD4+Vb6+ population led to an increase in lesion density indicating an atheroprotective and possible immunomodulatory role of the prevalent CD4+ T cell population in the early stages of lesion formation in ApoE mice. Funding: This study was supported by INSERM, UPMC Paris 6 and "Fondation de France'.
C O R T I S O L R E S P O N S E IN P A T I E N T S WITH CORONARY ARTERY DISEASE - RELATION TO INFLAMMATORY ACTIVITY
J. Nilm 1'2, A.G. Olsson 2, L. Jonasson 2. 1Research Center of Cardiovascular Disease, Division of Medicine, HOgland Hospital, Eksj5, Sweden." 2Dpt of Medicbte attcl Care, Facul~ of Health Sciences, LbtkOping Universi~, LbzkOping, Sweden Objective: A defective hypothalamic-pituitaxy adrenal (HPA) axis may lead to enhanced susceptibility to inflammatory disease. The aim of this study was to study the HPA axis activity in patients with coronary artery disease (CAD) and relate the findings to systemic inflammatory activity. M e t h o d : Thirty patients with CAD and 30 healthy controls were included. Salivary cortisol was repeatedly measured during 3 days and 24-hour urinary cortisol was collected. All subjects were subjected to physical and psychological stress tests. Salivary cortisol was measured before and 30 minutes after the tests. C-reactive protein (CRP) and intedeukin(IL)-6 were measured in serum. Result: The 24-hour urinary cortisol secretion was significantly higher in patients. The morning cortisol was similar in patients and controls while the evening cortisol was significantly higher in patients. I1-6 was correlated to evening cortisol (p< 0.01). The increase in cortisol was significantly larger in controls compared to patients after both physical and psycological stress tests (p< 0.01).The basline CRP did not differ between the 2 groups but increased significantly in patients 24 hours after the stress tests. Conclusion: CAD patients showed a defective HPA response, as evidenced by hypercortisolism, a flattened diurnal slope and a blunted cortisol response to acute stressors. The dysregulated cortisol pattern was associated with systemic inflammatory activity. A malfunction of neuroendocrine-immune mechanisms may contribute to the maintenance of inflammatory activity in CAD. Funding: This work was supported by grants from the Heaxt-Lung Foundation.
XIV bztenmtional Symposium on Atheroscletosis, Rome, Italy, June 18-22, 2006