- Email: [email protected]
PO15-417 ABSTRACT WITHDRAWN
Poster Sessions PO15 Endothelial function/markers
120
C-HL (n=20) and C-NL (n=20) - consisted of sex- and age–matched healthy individuals. Results: Both hyperlipidemic subjects and their normolipidemic relatives had significantly lower FMD (3.4±3.0% vs 6.3±2.8%, p<0.001, 5.2±2.3% vs 7.8±2.8%, p<0.01 respectively) compared to controls. In multivariate backward stepwise regression analysis, FMD in members of FCH families was independently associated with sex (p<0.001), age (p<0.01), C-peptide (p<0.05) and borderline with glycemia (p=0.052). FMD correlated inversely with IMT in all subjects of FCH families and in hyperlipidemic members. In multivariate backward stepwise regression analysis this relation remained independent (p<0.001, p<0.01 respectively). Conclusions: Members of families with familial combined hyperlipidemia show signs of endothelial dysfunction. Hyperlipidemic as well as normolipidemic relatives have a significantly lower FMD. The increase of IMT is evident only in hyperlipidemic subjects. Decreased FMD in normolipidemic individuals precedes IMT increase and may be caused by the present insulin resistance, which may precede the full expression of hyperlipidemia. This work was supported by grant IGA MZCR NR/9068-3.
ABSTRACT WITHDRAWN
PO15-418
GLYCATED LDL INDUCES ENDOTHELIAL DYSFUNCTION
L. Toma, C.S. Stancu, L.S. Niculescu, A.V. Sima. Lipoprotein and Atherosclerosis Department, Institute of Cellular Biology and Pathology, Bucharest, Romania The aim of the present study was to evaluate the effect of glycated LDL (gLDL) on endothelial cell dysfunction, primarily on the nitric oxide bioavailability. Methods: Human endothelial cells (EAhy926) were incubated with human gLDL in DMEM supplemented with 2% fetal calf serum, in the presence of either 1‰ or 4.5‰ glucose, for 24 h - 72 h. Glycated LDL was obtained by incubating LDL with 0.5 M glucose at 37°C, under sterile conditions, in the presence of EDTA and BHT. Nitric oxide and the total antioxidant capacity of the medium, cellular eNOS, CD36, LOX1 gene expression (by Real Time PCR), cholesterol esters (CE) accumulation, the reactive oxygen species (ROS) and the reactive nitrogen species (RNS) were quantified. Results: Results show that increased concentration of glucose and gLDL in the medium determine a statistically significant decrease of eNOS mRNA expression. Surprisingly, there was no variation in NOx levels in all employed conditions. Endothelial ROS and RNS concentrations were significantly increased after 72 hours of incubation with gLDL, as compared with control cells, a result which correlates with the decrease of the antioxidant capacity of the medium. Glycated LDL induced a 2 fold increase in the CE content, together with a significant increase of CD36 and LOX-1 gene expression. Conclusion: In conclusion, our data indicate that gLDL might be considered a risk factor in diabetes, because of the increase induced in the endothelial cells cholesterol content and oxidative stress, accompanied by a decrease of the eNOS gene expression. EFFECTS OF DRUGS ON ENDOTHELIAL DYSFUNCTION IN ANTIPHOSPHOLIPID SYNDROME
Belizna 1,2 ,
Lartigue 3 ,
Gilbert 3 ,
PO15-420
ENDOTHELIAL DYSFUNCTION ASSESSED BY PERIPHERAL ARTERIAL TONOMETRY (ENDO-PAT 2000) IN A HIGH CARDIOVASCULAR RISK POPULATION
R. Ferre, N. Plana, B. Coll, R. Cos, S. Parra, C. Alonso-Villaverde, A. Ameigide, A. Gonzalez, L. Masana. Vascular Medicine and Metabolism Unit. Hospital Sant Joan. Institut de Recerca En Ciències de La Salut. Universitat Rovira I Virgili, Reus, Spain
PO15-417
PO15-419
relaxing responses to acetylcholine or the NO donor nitroprusside after precontraction by phenylephrine. Five (out of 8) aPL reduced the response to acetylcholine compared to control mice. This effect was especially marked with 4b7 mAb. No changes in the response to nitroprusside were observed. The impairment was maintained after 3 weeks of treatment, and appeared related to a moderate decrease in NO mediated responses and a marked decrease in prostanoid-mediated relaxations. Endothelial dysfunction could be prevented by chronic treatment with statins or aspirin. Conclusions: A sub-population of aPL, cross-reacting with a nucleolar protein, directly and markedly alter endothelial function even in the absence of disease, and this might contribute to their proatherogenic and prothrombotic effects.
Tron 3 ,
Lévesque 1 ,
C.C. A. D. F. H. C. Thuillez 2 , V. Richard 2 . 1 Internal Medicine CHU Rouen, Rouen, 2 3 France; INSERM U644 Rouen, Rouen, France; Immunology Department Rouen, Rouen, France Objectives: Antiphospholipid antibodies (aPL) induce severe arterial lesions, and increase cardiovascular risk. This may be explained in part by an induction of endothelial dysfunction, but whether aPL may per se induce endothelial dysfunction in the absence of added disease is unknown. Methods and Results: CD1 mice received one single injection of IgG aPL derived from a male (BXSB x NZW)F1 mouse which develops a lupus-like disease associated with an antiphospholipid syndrome. One week later, first order mesenteric arteries (diameter 220-260μm) were isolated and mounted in a small vessel myograph for the measurement of
Background and Aims: Endothelial dysfunction is the primary defect leading to arteriosclerosis. It’s clinical assessment is difficult and mostly operator dependent. We aimed to study endothelial function by an operator independent method (ENDO-PAT 2000) in patients suffering from metabolic syndrome (MS) or HIV-infection. Methods: We studied 117 patients with high global cardiovascular risk (HCVR) or MS according to NCEP III criteria, 42 HIV-infected patients under stable highly active antiretroviral therapy, and 13 healthy subjects as controls. Clinical, anthropometrical and laboratory-related data were recorded. The endothelial function was assessed using Endo-Pat 2000. Briefly, this automated, operator-independent method measures NOdependent vascular response by peripheral arterial tonometry. Univariate analyses consisted in ANOVA for continuous variables and l 2 test for those categorical. Results: HCVR and HIV groups had impaired endothelial function compared to healthy population (Endo-PAT index 1.76, 1.84 and 2.13 respectively, p=0.002). Those patients in HCVR group who have MS exhibit worse endothelial function compared to patients without MS (Endo-Pat index 1.70 and 1.96, p=0.012). Using general lineal model, hypertriglyceridemia and abdominal perimeter were the factors determining endothelial dysfunction. Conclusions: HCVR, MS and HIV patients have endothelial dysfunction assessed by peripheral arterial tonometry when compared to healthy subjects. Hypertriglyceridemia and abdominal circumference are strong markers of endothelial dysfunction. ENDO-PAT 2000 is a reliable method to assess endothelial function. PO15-421
ASSYMETRIC DIMETHYLARGININE IN PATIENTS WITH SEVERE PERIPHERAL ARTERY DISEASE
H. Rusnakova 1 , H. Pittrova 1 , M. Cechura 2 , D. Rajdl 1 , L. Trefil 1 , H. Simandlova 2 , R. Pekna 1 , J. Racek 1 . 1 Institute of Clinical Biochemistry and Hematology, Pilsen, Czech Republic; 2 Department of Surgery, Charles University Hospital in Pilsen and Charles University, Medical Faculty in Pilsen, Pilsen, Czech Republic Assymetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthase and an independent risk factor of atherosclerosis. We aimed to reveal, whether patients with severe peripheral artery disease of lower extremities, have increased ADMA levels in comparison with controls. We enrolled 50 patients (14 women; median [interquartile range] age was 61.5 [57-68] years) admitted to the Department of Surgery in our hospital for scheduled bypass operation from indication of lower extremity arterial ischemic closure. Seventeen age-matched relatively healthy volunteers served as controls (10 women; age: 68 [60-72] years). Results are expressed as median [interquartile range]. Patients had similar concentrations of ADMA like controls (0.87 [0.80.94] μmol/l vs. 0.9 [0.77-1.11] μmol/l resp.; p=0.84). Homocysteine concentration was comparable in both groups (patients: 10.3 [8.53-13.45] μmol/l vs. controls: 10.8 [8.9-13.2] μmol/l; p=0.74). Patients had lower HDL-cholesterol (0.97 [0.89-1.26] mmol/l vs. 1.16 (1.03-1.31 mmol/l;
76th Congress of the European Atherosclerosis Society, June 10–13, 2007, Helsinki, Finland
120
C-HL (n=20) and C-NL (n=20) - consisted of sex- and age–matched healthy individuals. Results: Both hyperlipidemic subjects and their normolipidemic relatives had significantly lower FMD (3.4±3.0% vs 6.3±2.8%, p<0.001, 5.2±2.3% vs 7.8±2.8%, p<0.01 respectively) compared to controls. In multivariate backward stepwise regression analysis, FMD in members of FCH families was independently associated with sex (p<0.001), age (p<0.01), C-peptide (p<0.05) and borderline with glycemia (p=0.052). FMD correlated inversely with IMT in all subjects of FCH families and in hyperlipidemic members. In multivariate backward stepwise regression analysis this relation remained independent (p<0.001, p<0.01 respectively). Conclusions: Members of families with familial combined hyperlipidemia show signs of endothelial dysfunction. Hyperlipidemic as well as normolipidemic relatives have a significantly lower FMD. The increase of IMT is evident only in hyperlipidemic subjects. Decreased FMD in normolipidemic individuals precedes IMT increase and may be caused by the present insulin resistance, which may precede the full expression of hyperlipidemia. This work was supported by grant IGA MZCR NR/9068-3.
ABSTRACT WITHDRAWN
PO15-418
GLYCATED LDL INDUCES ENDOTHELIAL DYSFUNCTION
L. Toma, C.S. Stancu, L.S. Niculescu, A.V. Sima. Lipoprotein and Atherosclerosis Department, Institute of Cellular Biology and Pathology, Bucharest, Romania The aim of the present study was to evaluate the effect of glycated LDL (gLDL) on endothelial cell dysfunction, primarily on the nitric oxide bioavailability. Methods: Human endothelial cells (EAhy926) were incubated with human gLDL in DMEM supplemented with 2% fetal calf serum, in the presence of either 1‰ or 4.5‰ glucose, for 24 h - 72 h. Glycated LDL was obtained by incubating LDL with 0.5 M glucose at 37°C, under sterile conditions, in the presence of EDTA and BHT. Nitric oxide and the total antioxidant capacity of the medium, cellular eNOS, CD36, LOX1 gene expression (by Real Time PCR), cholesterol esters (CE) accumulation, the reactive oxygen species (ROS) and the reactive nitrogen species (RNS) were quantified. Results: Results show that increased concentration of glucose and gLDL in the medium determine a statistically significant decrease of eNOS mRNA expression. Surprisingly, there was no variation in NOx levels in all employed conditions. Endothelial ROS and RNS concentrations were significantly increased after 72 hours of incubation with gLDL, as compared with control cells, a result which correlates with the decrease of the antioxidant capacity of the medium. Glycated LDL induced a 2 fold increase in the CE content, together with a significant increase of CD36 and LOX-1 gene expression. Conclusion: In conclusion, our data indicate that gLDL might be considered a risk factor in diabetes, because of the increase induced in the endothelial cells cholesterol content and oxidative stress, accompanied by a decrease of the eNOS gene expression. EFFECTS OF DRUGS ON ENDOTHELIAL DYSFUNCTION IN ANTIPHOSPHOLIPID SYNDROME
Belizna 1,2 ,
Lartigue 3 ,
Gilbert 3 ,
PO15-420
ENDOTHELIAL DYSFUNCTION ASSESSED BY PERIPHERAL ARTERIAL TONOMETRY (ENDO-PAT 2000) IN A HIGH CARDIOVASCULAR RISK POPULATION
R. Ferre, N. Plana, B. Coll, R. Cos, S. Parra, C. Alonso-Villaverde, A. Ameigide, A. Gonzalez, L. Masana. Vascular Medicine and Metabolism Unit. Hospital Sant Joan. Institut de Recerca En Ciències de La Salut. Universitat Rovira I Virgili, Reus, Spain
PO15-417
PO15-419
relaxing responses to acetylcholine or the NO donor nitroprusside after precontraction by phenylephrine. Five (out of 8) aPL reduced the response to acetylcholine compared to control mice. This effect was especially marked with 4b7 mAb. No changes in the response to nitroprusside were observed. The impairment was maintained after 3 weeks of treatment, and appeared related to a moderate decrease in NO mediated responses and a marked decrease in prostanoid-mediated relaxations. Endothelial dysfunction could be prevented by chronic treatment with statins or aspirin. Conclusions: A sub-population of aPL, cross-reacting with a nucleolar protein, directly and markedly alter endothelial function even in the absence of disease, and this might contribute to their proatherogenic and prothrombotic effects.
Tron 3 ,
Lévesque 1 ,
C.C. A. D. F. H. C. Thuillez 2 , V. Richard 2 . 1 Internal Medicine CHU Rouen, Rouen, 2 3 France; INSERM U644 Rouen, Rouen, France; Immunology Department Rouen, Rouen, France Objectives: Antiphospholipid antibodies (aPL) induce severe arterial lesions, and increase cardiovascular risk. This may be explained in part by an induction of endothelial dysfunction, but whether aPL may per se induce endothelial dysfunction in the absence of added disease is unknown. Methods and Results: CD1 mice received one single injection of IgG aPL derived from a male (BXSB x NZW)F1 mouse which develops a lupus-like disease associated with an antiphospholipid syndrome. One week later, first order mesenteric arteries (diameter 220-260μm) were isolated and mounted in a small vessel myograph for the measurement of
Background and Aims: Endothelial dysfunction is the primary defect leading to arteriosclerosis. It’s clinical assessment is difficult and mostly operator dependent. We aimed to study endothelial function by an operator independent method (ENDO-PAT 2000) in patients suffering from metabolic syndrome (MS) or HIV-infection. Methods: We studied 117 patients with high global cardiovascular risk (HCVR) or MS according to NCEP III criteria, 42 HIV-infected patients under stable highly active antiretroviral therapy, and 13 healthy subjects as controls. Clinical, anthropometrical and laboratory-related data were recorded. The endothelial function was assessed using Endo-Pat 2000. Briefly, this automated, operator-independent method measures NOdependent vascular response by peripheral arterial tonometry. Univariate analyses consisted in ANOVA for continuous variables and l 2 test for those categorical. Results: HCVR and HIV groups had impaired endothelial function compared to healthy population (Endo-PAT index 1.76, 1.84 and 2.13 respectively, p=0.002). Those patients in HCVR group who have MS exhibit worse endothelial function compared to patients without MS (Endo-Pat index 1.70 and 1.96, p=0.012). Using general lineal model, hypertriglyceridemia and abdominal perimeter were the factors determining endothelial dysfunction. Conclusions: HCVR, MS and HIV patients have endothelial dysfunction assessed by peripheral arterial tonometry when compared to healthy subjects. Hypertriglyceridemia and abdominal circumference are strong markers of endothelial dysfunction. ENDO-PAT 2000 is a reliable method to assess endothelial function. PO15-421
ASSYMETRIC DIMETHYLARGININE IN PATIENTS WITH SEVERE PERIPHERAL ARTERY DISEASE
H. Rusnakova 1 , H. Pittrova 1 , M. Cechura 2 , D. Rajdl 1 , L. Trefil 1 , H. Simandlova 2 , R. Pekna 1 , J. Racek 1 . 1 Institute of Clinical Biochemistry and Hematology, Pilsen, Czech Republic; 2 Department of Surgery, Charles University Hospital in Pilsen and Charles University, Medical Faculty in Pilsen, Pilsen, Czech Republic Assymetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthase and an independent risk factor of atherosclerosis. We aimed to reveal, whether patients with severe peripheral artery disease of lower extremities, have increased ADMA levels in comparison with controls. We enrolled 50 patients (14 women; median [interquartile range] age was 61.5 [57-68] years) admitted to the Department of Surgery in our hospital for scheduled bypass operation from indication of lower extremity arterial ischemic closure. Seventeen age-matched relatively healthy volunteers served as controls (10 women; age: 68 [60-72] years). Results are expressed as median [interquartile range]. Patients had similar concentrations of ADMA like controls (0.87 [0.80.94] μmol/l vs. 0.9 [0.77-1.11] μmol/l resp.; p=0.84). Homocysteine concentration was comparable in both groups (patients: 10.3 [8.53-13.45] μmol/l vs. controls: 10.8 [8.9-13.2] μmol/l; p=0.74). Patients had lower HDL-cholesterol (0.97 [0.89-1.26] mmol/l vs. 1.16 (1.03-1.31 mmol/l;
76th Congress of the European Atherosclerosis Society, June 10–13, 2007, Helsinki, Finland