- Email: [email protected]
Apolipoprotein m modulates erythrocyte efflux and urinary excretion of sphingosine-1-phosphate
e176
Abstracts / Atherosclerosis 235 (2014) e84–e191
a
INTERNAL MEDICINE, HOSPITAL UNIVERSITARIO PUERTA DEL MAR CADIZ, CADIZ, Spain; b MEDICINE, MEDICINE FACULTY, CADIZ, Spain; c HOSPITAL CARLOS III , MADRID Objectives: The plasma concentration of HDL-C is currently considered as a protective factor for cardiovascular disease, and clinical should still be considered hypoalphalipoproteinemia as a risk factor for atherosclerosis. However, no scientific evidences to indicate the existence of different types of Hypoalphalipoproteinemias and the likelihood that some of them do not constitute a risk of complications of atherosclerosis. The objective of this study is to contribute to the knowledge of Hypoalphalipoproteinemias and optimize the selection of patients at risk.
Assuming the higher CIMT as representative of patientés risk, both HDL-c (Beta¼-0.158; p¼0.027; R2¼0.376) and ApoA-I (sBeta¼-0.146; p¼0.024; R2¼0.372) were inversely correlated to CIMT after adjustment for sex and age. In our population, LDL-C, ApoB, apoB/A-I ratio, TGs, chronic hyperglycemia, A1c, office blood pressure, hypertensive status, hsCRP or smoking did not show significant association with CIMT. Conclusion: Right and left CIMT are in close agreement with each other. After adjustment for sex and age, HDL-C and APOA-I were the main determinant factors of CIMT in subjects treated to target A1c and LDL-C. This study helps to clarify the recent doubts upon the main role of HDL-C in atherothrombotic disease. 30 - HDL metabolism
Methods: 882 medical records of consecutive patients evaluated for various reasons with analytic in the Hospital Universitario Puerta del Mar (Cádiz) were reviewed according to the criteria of low HDL cholesterol: less than 40 mg / dl (1.04 mmol / l) in men Results: The associated cardiovascular risk factors and the presence of cardiovascular disease (CVD) were collected. Results: In the study population, 49.6% had low plasma levels of HDL-C. The presence of coronary artery disease (CAD) was 14.4%, that of cerebral vascular disease (AVC) of 7.7%, the abdominal aortic aneurysm (AAA) of 0.7% and peripheral vascular disease (PVD) of 8.4%, simultaneously presenting plasma levels of HDL-C low percentage by 17.8, 7.9, 0.2 and 5.6% respectively. Statistically significant difference between patients with low and high plasma concentrations that had suffered EC and EVP were observed (p <0.003 and p <0.001 respectively). The presence of type 2 diabetes mellitus was 56% and a detailed comparative analysis of this subset of patients compared to non-diabetic shows statistically significant differences between the concentrations of low HDL-C, EC and EVP (p <0.001) Table2(no presented). Conclusion: The absence of specific clinical criteria suggests kinetic / HDL metabolic studies for a correct identification of patients with low HDL-C in cardiovascular disease risk. 30 - HDL metabolism EAS-0605. HDL-CHOLESTEROL AS THE MOST DETERMINANT METABOLIC FACTOR OF CAROTID INTIMA MEDIA THICKNESS IN A POPULATION UNDER TREATMENT C. Martínez, M. Fabregate, R. Fabregate, S. Tello-Blasco, C. Fernández, A. Andres, J. Saban-Ruiz Endothelial Pathology Unit, Hospital Ramon y Cajal, Madrid, Spain Objectives: The increase of Carotid Intima-Media Thickness (CIMT) has been related to cardiovascular risk factors (CVRF) and Coronary Artery Disease (CAD). We aim to evaluate the role of HDL-c and Apo-A1 in bilateral CIMT in patients treated to target LDL-c levels, as well as the impact on CMIT of haemodynamic, inflammatory and other metabolic factors. Methods: N¼171 patients with moderate-high cardiovacular risk, treated to target LDL-C, A1c and blood pressure according to 2011 ESC/EAS guidelines. Age: 57.6 (15.1) y.o.(range 18-85). 63.2 % hypertensives, 64.9% hyperglycemics; 51.5% with hypercholesterolemia,18.7 % smokers. Blood pressure: OMRON MI10IT. Biochemistry: HITACHI. ApoA-I, ApoB, hsCRP: Nephelometry. A1c: % (DCCT). Common carotid arteries Vivid S5, GE. Statistics: Continuous variables described as mean (Standard deviation). Significance: p<0.05. Student t-test. Agreement of means: BlandAltman plots (mean diffference 1.96*SD). Pearson's correlation. Multivariate linear regression models. SPSS, v15.0. Results: No significant differences were observed between paired right and left CIMTs. Both CIMTs showed a positive correlation (r¼0.496, p <0.001) and agreement (Bland-Altman-plot): only 6 subjects out of limits for rightleft difference, with no association between difference and mean. Both CIMTs became thicker with age: right-CIMT (r¼0.560; p<0.001), leftCIMT (r¼0.491; p<0.001).
EAS-1071. APOLIPOPROTEIN M MODULATES ERYTHROCYTE EFFLUX URINARY EXCRETION OF SPHINGOSINE-1-PHOSPHATE
AND
I. Suttera, R. Parkb, A. Othmanc, L. Rohrerc, T. Hornemannc, M. Stoffeld, O. Devuyste, A. von Eckardsteinf Clinical CHemistry, University of Zurich, Zurich, Switzerland; b Institute of Molecular Health Sciences, ETH Zurich, Zurich, Switzerland; c Clinical CHemistry, University of Zurich, Zurich, Switzerland; d Institute of Molecular Health Sciences, ETH Zurich, Zurich, Switzerland; e Physiology, University of Zurich, Zurich, Switzerland; f Clinical Chemistry, University of Zurich, Zurich, Switzerland
a
Objectives: Sphingosine-1-phosphate (S1P) mediates several cytoprotective functions of high density lipoproteins (HDL). Apolipoprotein M (apoM) acts as a specific S1P binding protein in HDL. Erythrocytes are the major source of S1P in plasma. After glomerular filtration apoM is endocytosed in the proximal tubules of the kidney. Methods: HDL of human plasma as well as HDL of wild-type, apoM-knockout (apoM-/-), and murine apoM transgenic mice (apoMtg) were compared for their ability to induce S1P efflux from washed human erythrocytes. Wild type and apoM-/- mice as well as three mouse strains with defective proximal tubule endocytosis were analysed for urinary excretion and plasma concentrations of S1P and apoM. Results: HDL of humans or mice elicited time- and dose-dependent S1P efflux from erythrocytes. S1P efflux was enhanced in the presence of HDL from apoMtg mice and reduced but not abolished in the presence of HDL from apoM-/- mice. S1P and apoM were not measurable in the urine of wild type mice. In contrast, ApoM-/- mice excreted significant amounts of S1P, and both apoM and S1P were detected in the urine of mice with a defective tubular endocytosis. However, in contrast to apoM-/- mice, which have reduced plasma levels of S1P, these mice showed normal plasma concentrations for apoM and S1P. Conclusion: HDL facilitates S1P efflux from erythrocytes by both apoMdependent and apoM-independent mechanisms. In addition, apoM facilitates tubular reabsorption of S1P from the urine, however with no impact on S1P plasma concentrations. 31 - Lipoprotein receptors EAS-0747. ROLE OF TYPE CLASS DEFECT ON LDL RECEPTOR ACTIVITY A. Benito-Vicentea, A. Etxebarriaa, L. Palaciosb, M. Stefb, H. Ostolazaa, C. Martina a Biochemistry and Molecular Biology, Unidad de Biofisica (CSIC UPV/EHU), Bilbao, Spain; b Progenika Biopharma, Progenika Bipharma, derio, Spain
Objectives: Familial Hypercholesterolemia is an autosomal dominant disorder mostly caused by mutations in the LDLR gene. LDLR comprises several domains that are responsible for the binding of its lipoprotein ligands, for the release of LDL in the endosome and for the interaction of LDLR with the clathrin endocytic-machinery. According to the nature
Abstracts / Atherosclerosis 235 (2014) e84–e191
a
INTERNAL MEDICINE, HOSPITAL UNIVERSITARIO PUERTA DEL MAR CADIZ, CADIZ, Spain; b MEDICINE, MEDICINE FACULTY, CADIZ, Spain; c HOSPITAL CARLOS III , MADRID Objectives: The plasma concentration of HDL-C is currently considered as a protective factor for cardiovascular disease, and clinical should still be considered hypoalphalipoproteinemia as a risk factor for atherosclerosis. However, no scientific evidences to indicate the existence of different types of Hypoalphalipoproteinemias and the likelihood that some of them do not constitute a risk of complications of atherosclerosis. The objective of this study is to contribute to the knowledge of Hypoalphalipoproteinemias and optimize the selection of patients at risk.
Assuming the higher CIMT as representative of patientés risk, both HDL-c (Beta¼-0.158; p¼0.027; R2¼0.376) and ApoA-I (sBeta¼-0.146; p¼0.024; R2¼0.372) were inversely correlated to CIMT after adjustment for sex and age. In our population, LDL-C, ApoB, apoB/A-I ratio, TGs, chronic hyperglycemia, A1c, office blood pressure, hypertensive status, hsCRP or smoking did not show significant association with CIMT. Conclusion: Right and left CIMT are in close agreement with each other. After adjustment for sex and age, HDL-C and APOA-I were the main determinant factors of CIMT in subjects treated to target A1c and LDL-C. This study helps to clarify the recent doubts upon the main role of HDL-C in atherothrombotic disease. 30 - HDL metabolism
Methods: 882 medical records of consecutive patients evaluated for various reasons with analytic in the Hospital Universitario Puerta del Mar (Cádiz) were reviewed according to the criteria of low HDL cholesterol: less than 40 mg / dl (1.04 mmol / l) in men Results: The associated cardiovascular risk factors and the presence of cardiovascular disease (CVD) were collected. Results: In the study population, 49.6% had low plasma levels of HDL-C. The presence of coronary artery disease (CAD) was 14.4%, that of cerebral vascular disease (AVC) of 7.7%, the abdominal aortic aneurysm (AAA) of 0.7% and peripheral vascular disease (PVD) of 8.4%, simultaneously presenting plasma levels of HDL-C low percentage by 17.8, 7.9, 0.2 and 5.6% respectively. Statistically significant difference between patients with low and high plasma concentrations that had suffered EC and EVP were observed (p <0.003 and p <0.001 respectively). The presence of type 2 diabetes mellitus was 56% and a detailed comparative analysis of this subset of patients compared to non-diabetic shows statistically significant differences between the concentrations of low HDL-C, EC and EVP (p <0.001) Table2(no presented). Conclusion: The absence of specific clinical criteria suggests kinetic / HDL metabolic studies for a correct identification of patients with low HDL-C in cardiovascular disease risk. 30 - HDL metabolism EAS-0605. HDL-CHOLESTEROL AS THE MOST DETERMINANT METABOLIC FACTOR OF CAROTID INTIMA MEDIA THICKNESS IN A POPULATION UNDER TREATMENT C. Martínez, M. Fabregate, R. Fabregate, S. Tello-Blasco, C. Fernández, A. Andres, J. Saban-Ruiz Endothelial Pathology Unit, Hospital Ramon y Cajal, Madrid, Spain Objectives: The increase of Carotid Intima-Media Thickness (CIMT) has been related to cardiovascular risk factors (CVRF) and Coronary Artery Disease (CAD). We aim to evaluate the role of HDL-c and Apo-A1 in bilateral CIMT in patients treated to target LDL-c levels, as well as the impact on CMIT of haemodynamic, inflammatory and other metabolic factors. Methods: N¼171 patients with moderate-high cardiovacular risk, treated to target LDL-C, A1c and blood pressure according to 2011 ESC/EAS guidelines. Age: 57.6 (15.1) y.o.(range 18-85). 63.2 % hypertensives, 64.9% hyperglycemics; 51.5% with hypercholesterolemia,18.7 % smokers. Blood pressure: OMRON MI10IT. Biochemistry: HITACHI. ApoA-I, ApoB, hsCRP: Nephelometry. A1c: % (DCCT). Common carotid arteries Vivid S5, GE. Statistics: Continuous variables described as mean (Standard deviation). Significance: p<0.05. Student t-test. Agreement of means: BlandAltman plots (mean diffference 1.96*SD). Pearson's correlation. Multivariate linear regression models. SPSS, v15.0. Results: No significant differences were observed between paired right and left CIMTs. Both CIMTs showed a positive correlation (r¼0.496, p <0.001) and agreement (Bland-Altman-plot): only 6 subjects out of limits for rightleft difference, with no association between difference and mean. Both CIMTs became thicker with age: right-CIMT (r¼0.560; p<0.001), leftCIMT (r¼0.491; p<0.001).
EAS-1071. APOLIPOPROTEIN M MODULATES ERYTHROCYTE EFFLUX URINARY EXCRETION OF SPHINGOSINE-1-PHOSPHATE
AND
I. Suttera, R. Parkb, A. Othmanc, L. Rohrerc, T. Hornemannc, M. Stoffeld, O. Devuyste, A. von Eckardsteinf Clinical CHemistry, University of Zurich, Zurich, Switzerland; b Institute of Molecular Health Sciences, ETH Zurich, Zurich, Switzerland; c Clinical CHemistry, University of Zurich, Zurich, Switzerland; d Institute of Molecular Health Sciences, ETH Zurich, Zurich, Switzerland; e Physiology, University of Zurich, Zurich, Switzerland; f Clinical Chemistry, University of Zurich, Zurich, Switzerland
a
Objectives: Sphingosine-1-phosphate (S1P) mediates several cytoprotective functions of high density lipoproteins (HDL). Apolipoprotein M (apoM) acts as a specific S1P binding protein in HDL. Erythrocytes are the major source of S1P in plasma. After glomerular filtration apoM is endocytosed in the proximal tubules of the kidney. Methods: HDL of human plasma as well as HDL of wild-type, apoM-knockout (apoM-/-), and murine apoM transgenic mice (apoMtg) were compared for their ability to induce S1P efflux from washed human erythrocytes. Wild type and apoM-/- mice as well as three mouse strains with defective proximal tubule endocytosis were analysed for urinary excretion and plasma concentrations of S1P and apoM. Results: HDL of humans or mice elicited time- and dose-dependent S1P efflux from erythrocytes. S1P efflux was enhanced in the presence of HDL from apoMtg mice and reduced but not abolished in the presence of HDL from apoM-/- mice. S1P and apoM were not measurable in the urine of wild type mice. In contrast, ApoM-/- mice excreted significant amounts of S1P, and both apoM and S1P were detected in the urine of mice with a defective tubular endocytosis. However, in contrast to apoM-/- mice, which have reduced plasma levels of S1P, these mice showed normal plasma concentrations for apoM and S1P. Conclusion: HDL facilitates S1P efflux from erythrocytes by both apoMdependent and apoM-independent mechanisms. In addition, apoM facilitates tubular reabsorption of S1P from the urine, however with no impact on S1P plasma concentrations. 31 - Lipoprotein receptors EAS-0747. ROLE OF TYPE CLASS DEFECT ON LDL RECEPTOR ACTIVITY A. Benito-Vicentea, A. Etxebarriaa, L. Palaciosb, M. Stefb, H. Ostolazaa, C. Martina a Biochemistry and Molecular Biology, Unidad de Biofisica (CSIC UPV/EHU), Bilbao, Spain; b Progenika Biopharma, Progenika Bipharma, derio, Spain
Objectives: Familial Hypercholesterolemia is an autosomal dominant disorder mostly caused by mutations in the LDLR gene. LDLR comprises several domains that are responsible for the binding of its lipoprotein ligands, for the release of LDL in the endosome and for the interaction of LDLR with the clathrin endocytic-machinery. According to the nature