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Expression of fractalkine and its receptor (CX3CR1) in subcutanous adipose tissue from patients with coronary artery disease and type 2 diabetes.
Abstracts / Atherosclerosis 235 (2014) e192–e301
Atherosclerosis was quantified en face as % aortic plaque area (APA) in Sudan IV-stained aortas. To evaluate group differences, one-way ANOVA was applied, followed by a post-hoc Tukey's test. Results: In the three groups (CD, HFD-D and HFD), the results were as follows (medians and interquartile range): CrP: 8.06 microg/ml (5.9211.99), 15.65 (11.95-38.40), 19.80 (12.43-69.78); GLU: 3.2 mmol/L (2.8-3.3), 5.0 (3.6-10.4), 2.7 (2.2-3.0); FRA: 226 micromol/L (209-237), 382 (298444), 239 (212-252); TC 2 mmol/L (1.7-2.9), 21.0 (16.6-23.7), 21.6 (11.230.4); TG: 0.33 mmol/L (0.27-0.57), 1.41 (0.89-1.86), 1.26 (0.62-2.75); OxLDL: 9.1 U/L (7.3-11.7), 42.6 (30.4-60.0), 49.9 (26.4-67.1); APA: 0%, 34% (25-54), 39% (29-63). In HFD and HFD-D, CrP, TC, TG, oxLDL, and APA were significantly higher (p<0.05 or less) compared to CD whereas GLU and FRA were significantly higher in the HFD-D group compared to both HFD and CD. Conclusion: In this study, a new minipig model for atherosclerosis is presented with levels of APA comparable to other porcine models. No effect of mild diabetes was found. Further elucidating the role of inflammation and metabolic changes is a perspective. 57 - Diabetes and metabolic syndrome EAS-0781. ENHANCED LEVELS OF THE LIGHT/LYMPHOTOXIN-BETA RECEPTOR INFLAMMATORY AXIS IN METABOLIC SYNDROME PATIENTS S. Martínez-Hervása, I. Andrés-Blascob, A. Vinuéb, A. Herrerob, L. Piquerasb, J.F. Ascasoa, M.J. Sanzc, H. González-Navarrod a Endocrinology and Nutrition, Fundacion Para la Investigacion DelhospitalClinico de Valencia-Incliva, Valencia, Spain; b Pharmacology, Fundacion Para la Investigacion Delhospital-Clinico de Valencia-Incliva, Valencia, Spain; c Pharmacology, University of Valencia, Valencia, Spain; d Pharmacology, Fundación para la investigación Hospital Clinico de Valencia-INCLIVA, Valencia, Spain
Objectives: Metabolic syndrome (MetS) is a major risk factor for developing cardiovascular disease (CVD) and atherosclerosis. Activation of the immune system and secretion of inflammatory mediators promotes the progression of atheroma plaques. Previous studies have reported expression of the cytokine LIGHT (TNFSF14) in human atheroma plaques and a role in promoting foam cell formation. The aim of the present study was to investigate the relationship between the expression of LIGHT and its receptor, Lymphotoxin b receptor (LTb-R), and the development of atherosclerosis in patients exhibiting different factors of the MetS.
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57 - Diabetes and metabolic syndrome EAS-0745. EXPRESSION OF FRACTALKINE AND ITS RECEPTOR (CX3CR1) IN SUBCUTANOUS ADIPOSE TISSUE FROM PATIENTS WITH CORONARY ARTERY DISEASE AND TYPE 2 DIABETES. I. Njervea, R. Byrkjelanda, H. Arnesena, S. Åkraa, S. Solheima, I. Seljeflota a
Department of Cardiology, Oslo University Hospital Ullevaal, Oslo, Norway
Objectives: The chemokine fractalkine and it’s receptor CX3CR1, are associated with inflammation and atherosclerosis. Fractalkine is expressed in endothelial cells, macrophages and adipocytes amongst others. Conflicting results regarding associations between fractalkine levels and coronary artery disease (CAD) and glucometabolic state exists. We aimed to investige whether there are any associations between glucometabolic control (HbA1c), insulin resistance (HOMA2-IR), BMI and the inflammatory markers fractalkine and MCP-1 in patients with both CAD and type 2 diabetes. Methods: Venous blood samples and gluteal subcutanous adipose tissue samples were collected in the morning after an overnight fast in 137 patients with both CAD and type 2 diabetes. Circulating fractalkine and MCP1 was determined by ELISAs. Gene expression (mRNA) in the adipose tissue of the same markers and CX3CR1 were analyzed by rt-PCR (Viia TM 7 Real Time PCR System), and quantified in relation to a reference sample. Results: (median (25, 75 percentile): HbA1c level was 7.4 (6.8, 8.3)%, insulin 57.0 (33.0, 101.5) pmol/L, C-peptide 966 (713, 1290) pmol/L, HOMA2-IR 1.3 (0.7, 2.1) and BMI 28.7 (25.7, 31.6) kg/m2. Circulating fractalkine level was 474 (366, 591) pg/mL and MCP-1 270 (233, 308) pg/mL (weakly correlated with each other (r¼0.220, p¼0.010)). HbA1c was weakly, inversely correlated with fractalkine levels (r¼-0.211, p¼0.013). We found no significant correlations between the genetic expression of MCP-1, fractalkine or CX3CR1 in adipose tissue and the glucometabolic variables. However, the expression of CX3CR1 correlated with BMI (r¼0.378, p<0.001) Conclusion: No significant correlations were found between the selected glucometabolic variables and circulating as well as adipose tissue mRNA levels of fractalkine. The correlation between CX3CR1 expression and BMI may represent a connection between expanding adipose tissue mass and low grade inflammation, but further investigations are needed. 57 - Diabetes and metabolic syndrome
Methods: Unrelated 152 individuals were selected by opportunistic method in a cross-sectional study following the definitions of the National Cholesterol Education Program-Adult Treatment Panel (ATP)III and divided as controls, MetS and MetS patients with insulin resistance (MetSIR). Plasmatic parameters were determined after overnight fasting and circulating leukocytes were isolated for real time PCR expression studies. Atherosclerosis was assessed by the common carotid intima-media thickness (CC-IMT) by B-mode ultrasound. Results: Compared to controls, MetS and MetS-IR subjects exhibited increased fasting glucose, triglycerides, apoB levels, sistolic and diastolic blood presure and body mass index. As expected MetS-IR subjects had higher insulin levels and HOMA index than MetS patients. No differences in age or LDL-Cholesterol were found among the groups. CC-IMT was enhanced in both MetS and MetS-IR compared to controls (0.687, 0.680 vs 0.524, p<0.001) without differences between MetS and MetS-IR patients. mRNA expression studies showed increased LIGHT/LTb-R axis in MetS (p<0.02 and p<0.05) and MetS-IR patients (p<0.04 and 0.02) compared to control subjects. As before, expression levels were similar in MetS and MetS-IR. Conclusion: Increased atherosclerosis in MetS patients is associated to higher LIGHT/LTb-R axis expression in circulating leukocytes. These results suggest that modulation of this inflamatory pathway might be of use in therapies targeted to limit atherosclerosis progression in MetS patients.
EAS-0896. CARDIOMETABOLIC RISK ASSOCIATED WITH METABOLIC SYNDROME IN TYPE 2 DIABETES PATIENTS M. Torreaa, N. Aladeazabala, O.L.G.A. Lopez Berasteguia, B. Pinillaa, A. Muiñoa, J. Millana a
Internal Medicine, HGU Gregorio Marañón, Madrid, Spain
Objectives: Diabetes Mellitus is associated with a high cardiovascular morbi-mortality. This feature is related with macrovascular and microvascular complications. Metabolic syndrome, a clinical condition with high risk that is present frequently in diabetic patients may be a factor that increase the risk. This study was made to detect differences in the estimated risk in diabetic patients depending of presence/absence of metabolic syndrome. Methods: We have studied a group of patients with type 2 DM (n¼80) that were attended in primary care. Diagnosis of metabolic syndrome was made according with ATPIII criteria and IDF criteria. Cardiovascular risk was calculated according with Framingham scale. Results: In patients with tipo 2 DM metabolic syndrome was found in 47,5 % (ATPIII) and 49 % (IDF). Cardiovascular risk (Framingham) up to 20 % was
Atherosclerosis was quantified en face as % aortic plaque area (APA) in Sudan IV-stained aortas. To evaluate group differences, one-way ANOVA was applied, followed by a post-hoc Tukey's test. Results: In the three groups (CD, HFD-D and HFD), the results were as follows (medians and interquartile range): CrP: 8.06 microg/ml (5.9211.99), 15.65 (11.95-38.40), 19.80 (12.43-69.78); GLU: 3.2 mmol/L (2.8-3.3), 5.0 (3.6-10.4), 2.7 (2.2-3.0); FRA: 226 micromol/L (209-237), 382 (298444), 239 (212-252); TC 2 mmol/L (1.7-2.9), 21.0 (16.6-23.7), 21.6 (11.230.4); TG: 0.33 mmol/L (0.27-0.57), 1.41 (0.89-1.86), 1.26 (0.62-2.75); OxLDL: 9.1 U/L (7.3-11.7), 42.6 (30.4-60.0), 49.9 (26.4-67.1); APA: 0%, 34% (25-54), 39% (29-63). In HFD and HFD-D, CrP, TC, TG, oxLDL, and APA were significantly higher (p<0.05 or less) compared to CD whereas GLU and FRA were significantly higher in the HFD-D group compared to both HFD and CD. Conclusion: In this study, a new minipig model for atherosclerosis is presented with levels of APA comparable to other porcine models. No effect of mild diabetes was found. Further elucidating the role of inflammation and metabolic changes is a perspective. 57 - Diabetes and metabolic syndrome EAS-0781. ENHANCED LEVELS OF THE LIGHT/LYMPHOTOXIN-BETA RECEPTOR INFLAMMATORY AXIS IN METABOLIC SYNDROME PATIENTS S. Martínez-Hervása, I. Andrés-Blascob, A. Vinuéb, A. Herrerob, L. Piquerasb, J.F. Ascasoa, M.J. Sanzc, H. González-Navarrod a Endocrinology and Nutrition, Fundacion Para la Investigacion DelhospitalClinico de Valencia-Incliva, Valencia, Spain; b Pharmacology, Fundacion Para la Investigacion Delhospital-Clinico de Valencia-Incliva, Valencia, Spain; c Pharmacology, University of Valencia, Valencia, Spain; d Pharmacology, Fundación para la investigación Hospital Clinico de Valencia-INCLIVA, Valencia, Spain
Objectives: Metabolic syndrome (MetS) is a major risk factor for developing cardiovascular disease (CVD) and atherosclerosis. Activation of the immune system and secretion of inflammatory mediators promotes the progression of atheroma plaques. Previous studies have reported expression of the cytokine LIGHT (TNFSF14) in human atheroma plaques and a role in promoting foam cell formation. The aim of the present study was to investigate the relationship between the expression of LIGHT and its receptor, Lymphotoxin b receptor (LTb-R), and the development of atherosclerosis in patients exhibiting different factors of the MetS.
e237
57 - Diabetes and metabolic syndrome EAS-0745. EXPRESSION OF FRACTALKINE AND ITS RECEPTOR (CX3CR1) IN SUBCUTANOUS ADIPOSE TISSUE FROM PATIENTS WITH CORONARY ARTERY DISEASE AND TYPE 2 DIABETES. I. Njervea, R. Byrkjelanda, H. Arnesena, S. Åkraa, S. Solheima, I. Seljeflota a
Department of Cardiology, Oslo University Hospital Ullevaal, Oslo, Norway
Objectives: The chemokine fractalkine and it’s receptor CX3CR1, are associated with inflammation and atherosclerosis. Fractalkine is expressed in endothelial cells, macrophages and adipocytes amongst others. Conflicting results regarding associations between fractalkine levels and coronary artery disease (CAD) and glucometabolic state exists. We aimed to investige whether there are any associations between glucometabolic control (HbA1c), insulin resistance (HOMA2-IR), BMI and the inflammatory markers fractalkine and MCP-1 in patients with both CAD and type 2 diabetes. Methods: Venous blood samples and gluteal subcutanous adipose tissue samples were collected in the morning after an overnight fast in 137 patients with both CAD and type 2 diabetes. Circulating fractalkine and MCP1 was determined by ELISAs. Gene expression (mRNA) in the adipose tissue of the same markers and CX3CR1 were analyzed by rt-PCR (Viia TM 7 Real Time PCR System), and quantified in relation to a reference sample. Results: (median (25, 75 percentile): HbA1c level was 7.4 (6.8, 8.3)%, insulin 57.0 (33.0, 101.5) pmol/L, C-peptide 966 (713, 1290) pmol/L, HOMA2-IR 1.3 (0.7, 2.1) and BMI 28.7 (25.7, 31.6) kg/m2. Circulating fractalkine level was 474 (366, 591) pg/mL and MCP-1 270 (233, 308) pg/mL (weakly correlated with each other (r¼0.220, p¼0.010)). HbA1c was weakly, inversely correlated with fractalkine levels (r¼-0.211, p¼0.013). We found no significant correlations between the genetic expression of MCP-1, fractalkine or CX3CR1 in adipose tissue and the glucometabolic variables. However, the expression of CX3CR1 correlated with BMI (r¼0.378, p<0.001) Conclusion: No significant correlations were found between the selected glucometabolic variables and circulating as well as adipose tissue mRNA levels of fractalkine. The correlation between CX3CR1 expression and BMI may represent a connection between expanding adipose tissue mass and low grade inflammation, but further investigations are needed. 57 - Diabetes and metabolic syndrome
Methods: Unrelated 152 individuals were selected by opportunistic method in a cross-sectional study following the definitions of the National Cholesterol Education Program-Adult Treatment Panel (ATP)III and divided as controls, MetS and MetS patients with insulin resistance (MetSIR). Plasmatic parameters were determined after overnight fasting and circulating leukocytes were isolated for real time PCR expression studies. Atherosclerosis was assessed by the common carotid intima-media thickness (CC-IMT) by B-mode ultrasound. Results: Compared to controls, MetS and MetS-IR subjects exhibited increased fasting glucose, triglycerides, apoB levels, sistolic and diastolic blood presure and body mass index. As expected MetS-IR subjects had higher insulin levels and HOMA index than MetS patients. No differences in age or LDL-Cholesterol were found among the groups. CC-IMT was enhanced in both MetS and MetS-IR compared to controls (0.687, 0.680 vs 0.524, p<0.001) without differences between MetS and MetS-IR patients. mRNA expression studies showed increased LIGHT/LTb-R axis in MetS (p<0.02 and p<0.05) and MetS-IR patients (p<0.04 and 0.02) compared to control subjects. As before, expression levels were similar in MetS and MetS-IR. Conclusion: Increased atherosclerosis in MetS patients is associated to higher LIGHT/LTb-R axis expression in circulating leukocytes. These results suggest that modulation of this inflamatory pathway might be of use in therapies targeted to limit atherosclerosis progression in MetS patients.
EAS-0896. CARDIOMETABOLIC RISK ASSOCIATED WITH METABOLIC SYNDROME IN TYPE 2 DIABETES PATIENTS M. Torreaa, N. Aladeazabala, O.L.G.A. Lopez Berasteguia, B. Pinillaa, A. Muiñoa, J. Millana a
Internal Medicine, HGU Gregorio Marañón, Madrid, Spain
Objectives: Diabetes Mellitus is associated with a high cardiovascular morbi-mortality. This feature is related with macrovascular and microvascular complications. Metabolic syndrome, a clinical condition with high risk that is present frequently in diabetic patients may be a factor that increase the risk. This study was made to detect differences in the estimated risk in diabetic patients depending of presence/absence of metabolic syndrome. Methods: We have studied a group of patients with type 2 DM (n¼80) that were attended in primary care. Diagnosis of metabolic syndrome was made according with ATPIII criteria and IDF criteria. Cardiovascular risk was calculated according with Framingham scale. Results: In patients with tipo 2 DM metabolic syndrome was found in 47,5 % (ATPIII) and 49 % (IDF). Cardiovascular risk (Framingham) up to 20 % was