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Serum levels of lipoprotein-associated phospholipase A2 in patients with peripheral arterial disease
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Abstracts / Atherosclerosis 241 (2015) e149ee229
Results: Almost 1500 secretome proteins were identified. First standard classification of proteins with fold change greater than two revealed 163 differentially regulated proteins between AAD and AVR, 96 between AAD and TAA as well as 25 between AVR and TAA. Further computational analysis via regularized classification based on fold change identified platelet factor 4, intelectin-1 and platelet basic protein as the best discriminating between AAD and both control groups. In the following steps, biochemical validation of these selected biomarker candidate will performed in blood samples. Conclusions: The newly identified biomarker candidates may be of clinical interest in the prognostic monitoring of patients at increased risk for AAD, for example patients with Marfan syndrome or with TAA. Arteriopathy EAS-0978. SERUM LEVELS OF LIPOPROTEIN-ASSOCIATED PHOSPHOLIPASE A2 IN PATIENTS WITH PERIPHERAL ARTERIAL DISEASE J. Petrkova 1, *, Z. Navratilova 2, M. Petrek 3, P. Martin 4. 1 Internal Medicine Cardiology, Palacky University Faculty of Medicine and Dentistry, Olomouc, Czech Republic; 2 Pathological Physiology, Palacky University Faculty of Medicine and Dentistry, Olomouc, Czech Republic; 3 Institute of Molecular and Translational Medicine, Palacky University Faculty of Medicine and Dentistry, Olomouc, Czech Republic; 4 Clinical and Molecular Pathology, University Hospital Olomouc, Olomouc, Czech Republic
* Corresponding author. Background and aim: Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a vascular specific enzyme expressed in atherosclerotic plaques. Elevated Lp-PLA2 levels have been linked with increased risk of coronary artery disease and/or ischemic stroke. However, there have been little information about Lp-PLA2 in patients with peripheral arterial disease (PAD). We have, therefore, determined serum Lp-PLA2 in PAD patients and compared it with levels observed in healthy control subjects, and also within the patient group. Methods: Lp-PLA2 was determined by an enzyme linked immunosorbent assay („PLAC test', diaDexus, San Francisco, CA) in serum from 33 patients with PAD and 98 control healthy subjects of Czech ethnicity, who provided informed written consent according to approval by Institutional Ethics Committee. Results: Lp-PLA2 levels (ng/ml) were increased in PAD patients (median ± SEM: 443±20 ng/ml) compared to the control group (366±5 ng/ml; p<0.001).The highest Lp-PLA2 levels (537±28 ng/ml) were detected in patients with Fontaine 2a classification stage. Conclusion: Reported elevation of Lp-PLA2 in patients with peripheral arterial disease and observed association with disease clinical course suggest a possible involvement of Lp-PLA2 in development of atherosclerotic inflammation also in PAD. Plausible implication of Lp-PLA2 as a potential biomarker for supplementary diagnostics of peripheral atherosclerosis must be investigated in extended patient cohorts. Grant support: IGA PU LF 2015_020, LO1304.
Lifestyle and CV risk EAS-0157. EFFECT OF WEIGHT LOSS AND EXERCISE ON THE HIGH-DENSITY LIPOPROTEIN (HDL) LIPIDOME IN INDIVIDUALS WITH METABOLIC SYNDROME (METS) A. Khan 1, *, P. Nestel 2, N. Straznicky 3, P. Mundra 1, K. Huynh 1, N. Mellett 1, G. Wong 1, J. Weir 1, C. Barlow 1, T. NG 1, B. Kingwell 4, P. Meikle 1. 1 Metabolomics Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, Australia; 2 Lipoproteins and Atherosclerosis Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, Australia; 3 Human Neurotransmitters Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, Australia; 4 Metabolic and Vascular Physiology Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, Australia
* Corresponding author. Aim: Weight loss and exercise interventions are recommended to raise HDL-cholesterol and attenuate disease risk. The effects of lifestyle changes on HDL lipidome have not been elucidated. We aim to determine the effect of lifestyle changes on the bioactive lipid constituents of HDL beyond cholesterol. Methods: Individuals with MetS (n¼95) were matched for age and sex with a group of healthy controls (n¼40). The MetS group were randomized to one of three 12 week interventions i) dietary weight loss (n¼19) ii) dietary weight loss with exercise (n¼17) or iii) control MetS (n¼17). HDL fractions were isolated using sequential ultracentrifugation. HDL lipidome (334 species) were analysed by liquid chromatography-tandem mass spectrometry. Differences between MetS and controls and the effect of treatment (change from baseline) were examined. Results: HDL from MetS showed elevated di- and triacylglycerol and lysophospholipids, whereas ceramides, mono, di- and trihexosylceramide, sphingomyelin; and the alkyl- and alkenylphospholipid lipid classes were lower (p <0.05, Benjamini-Hochberg corrected). Following dietary weight loss, multiple lipids showed a trend towards the healthy control group with significant changes in alkylphosphatidylcholine and alkenylphosphatidylcholine. Weight loss with exercise typically showed a stronger effect with significant changes in alkylphosphatidylcholine as well as diand trihexosylceramide. Conclusions: The HDL lipidome is altered in MetS. Lifestyle interventions modified the HDL lipidome beyond HDL-cholesterol towards the profile observed in healthy controls, with the greatest effect observed for weight loss combined with exercise. This knowledge will inform the development of HDL raising therapies targeting patients at risk for T2D and CVD.
EAS-0305. STRENGTH-ENDURANCE TRAINING MAY PROMOTE PRO-ATHEROGENIC CHANGES IN LIPOPROTEIN PROFILE OF ADOLESCENT ROWERS D. Turowski 1, A. Pokrywka 2, W. Braksator 3, J. Rysz 4, M. Banach 5, *. 1 Department of Biochemistry, Institute of Sport, Warsaw, Poland; 2 Department of Anti-Doping Research, Institute of Sport, Warsaw, Poland; 3 Department of Cardiology Hypertension and Internal Medicine, Warsaw Medical University, Warsaw, Poland; 4 Department of Nephrology Hypertension and Family Medicine, Medical University of Lodz, Lodz, Poland; 5 Department of Hypertension, Medical University of Lodz, Lodz, Poland
* Corresponding author. Aim: Physical exercise beneficially modifies CV risk by decreasing atherogenic lipoproteins in the blood. LDL particles play a key role in initiation and progression of atherosclerosis. However, little is known about the influence of various types of exercise training on LDL subfraction profile in athletes atthe beginning of professional career. Method: The study was performed in the group of young males: 37 rowers (at age 14,4±1,1 years) and 29 football players(14,7±2,1 years) within 3-month sport-specific training varying in exercise loads (IIIC vs IC according to Mitchell’s classification respectively).Blood lipid profile with LDL according to Friedewald’s formula and proportion of HDL, VLDL and LDL subfractions were assessed respectively by spectrophotometry (Pentra 400 Horiba) and electrophoresis methods (Lipoprint Quantimetrix). Results: Total LDL significantly increased in both groups: 63,1±18,3 mg% vs. 72,3±23,9 p<0,001 (rowers) and 70,1±15,9 mg% vs.81,1±14,7 mg% p<0,005 (football players). TC/HDL ratio increased only in rowers: 2,6±0,5vs. 2,8±0,6 p<0,005. Significant shifts in proportions of lipoprotein fractions differed in both groups by electrophoresis. Although more pronounced changes were related to LDL subfractions in football players, the number ofathletes with more atherogenic subfractions (LDL-3 and LDL-4) increased almost twice in rowers (table).
Abstracts / Atherosclerosis 241 (2015) e149ee229
Results: Almost 1500 secretome proteins were identified. First standard classification of proteins with fold change greater than two revealed 163 differentially regulated proteins between AAD and AVR, 96 between AAD and TAA as well as 25 between AVR and TAA. Further computational analysis via regularized classification based on fold change identified platelet factor 4, intelectin-1 and platelet basic protein as the best discriminating between AAD and both control groups. In the following steps, biochemical validation of these selected biomarker candidate will performed in blood samples. Conclusions: The newly identified biomarker candidates may be of clinical interest in the prognostic monitoring of patients at increased risk for AAD, for example patients with Marfan syndrome or with TAA. Arteriopathy EAS-0978. SERUM LEVELS OF LIPOPROTEIN-ASSOCIATED PHOSPHOLIPASE A2 IN PATIENTS WITH PERIPHERAL ARTERIAL DISEASE J. Petrkova 1, *, Z. Navratilova 2, M. Petrek 3, P. Martin 4. 1 Internal Medicine Cardiology, Palacky University Faculty of Medicine and Dentistry, Olomouc, Czech Republic; 2 Pathological Physiology, Palacky University Faculty of Medicine and Dentistry, Olomouc, Czech Republic; 3 Institute of Molecular and Translational Medicine, Palacky University Faculty of Medicine and Dentistry, Olomouc, Czech Republic; 4 Clinical and Molecular Pathology, University Hospital Olomouc, Olomouc, Czech Republic
* Corresponding author. Background and aim: Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a vascular specific enzyme expressed in atherosclerotic plaques. Elevated Lp-PLA2 levels have been linked with increased risk of coronary artery disease and/or ischemic stroke. However, there have been little information about Lp-PLA2 in patients with peripheral arterial disease (PAD). We have, therefore, determined serum Lp-PLA2 in PAD patients and compared it with levels observed in healthy control subjects, and also within the patient group. Methods: Lp-PLA2 was determined by an enzyme linked immunosorbent assay („PLAC test', diaDexus, San Francisco, CA) in serum from 33 patients with PAD and 98 control healthy subjects of Czech ethnicity, who provided informed written consent according to approval by Institutional Ethics Committee. Results: Lp-PLA2 levels (ng/ml) were increased in PAD patients (median ± SEM: 443±20 ng/ml) compared to the control group (366±5 ng/ml; p<0.001).The highest Lp-PLA2 levels (537±28 ng/ml) were detected in patients with Fontaine 2a classification stage. Conclusion: Reported elevation of Lp-PLA2 in patients with peripheral arterial disease and observed association with disease clinical course suggest a possible involvement of Lp-PLA2 in development of atherosclerotic inflammation also in PAD. Plausible implication of Lp-PLA2 as a potential biomarker for supplementary diagnostics of peripheral atherosclerosis must be investigated in extended patient cohorts. Grant support: IGA PU LF 2015_020, LO1304.
Lifestyle and CV risk EAS-0157. EFFECT OF WEIGHT LOSS AND EXERCISE ON THE HIGH-DENSITY LIPOPROTEIN (HDL) LIPIDOME IN INDIVIDUALS WITH METABOLIC SYNDROME (METS) A. Khan 1, *, P. Nestel 2, N. Straznicky 3, P. Mundra 1, K. Huynh 1, N. Mellett 1, G. Wong 1, J. Weir 1, C. Barlow 1, T. NG 1, B. Kingwell 4, P. Meikle 1. 1 Metabolomics Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, Australia; 2 Lipoproteins and Atherosclerosis Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, Australia; 3 Human Neurotransmitters Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, Australia; 4 Metabolic and Vascular Physiology Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, Australia
* Corresponding author. Aim: Weight loss and exercise interventions are recommended to raise HDL-cholesterol and attenuate disease risk. The effects of lifestyle changes on HDL lipidome have not been elucidated. We aim to determine the effect of lifestyle changes on the bioactive lipid constituents of HDL beyond cholesterol. Methods: Individuals with MetS (n¼95) were matched for age and sex with a group of healthy controls (n¼40). The MetS group were randomized to one of three 12 week interventions i) dietary weight loss (n¼19) ii) dietary weight loss with exercise (n¼17) or iii) control MetS (n¼17). HDL fractions were isolated using sequential ultracentrifugation. HDL lipidome (334 species) were analysed by liquid chromatography-tandem mass spectrometry. Differences between MetS and controls and the effect of treatment (change from baseline) were examined. Results: HDL from MetS showed elevated di- and triacylglycerol and lysophospholipids, whereas ceramides, mono, di- and trihexosylceramide, sphingomyelin; and the alkyl- and alkenylphospholipid lipid classes were lower (p <0.05, Benjamini-Hochberg corrected). Following dietary weight loss, multiple lipids showed a trend towards the healthy control group with significant changes in alkylphosphatidylcholine and alkenylphosphatidylcholine. Weight loss with exercise typically showed a stronger effect with significant changes in alkylphosphatidylcholine as well as diand trihexosylceramide. Conclusions: The HDL lipidome is altered in MetS. Lifestyle interventions modified the HDL lipidome beyond HDL-cholesterol towards the profile observed in healthy controls, with the greatest effect observed for weight loss combined with exercise. This knowledge will inform the development of HDL raising therapies targeting patients at risk for T2D and CVD.
EAS-0305. STRENGTH-ENDURANCE TRAINING MAY PROMOTE PRO-ATHEROGENIC CHANGES IN LIPOPROTEIN PROFILE OF ADOLESCENT ROWERS D. Turowski 1, A. Pokrywka 2, W. Braksator 3, J. Rysz 4, M. Banach 5, *. 1 Department of Biochemistry, Institute of Sport, Warsaw, Poland; 2 Department of Anti-Doping Research, Institute of Sport, Warsaw, Poland; 3 Department of Cardiology Hypertension and Internal Medicine, Warsaw Medical University, Warsaw, Poland; 4 Department of Nephrology Hypertension and Family Medicine, Medical University of Lodz, Lodz, Poland; 5 Department of Hypertension, Medical University of Lodz, Lodz, Poland
* Corresponding author. Aim: Physical exercise beneficially modifies CV risk by decreasing atherogenic lipoproteins in the blood. LDL particles play a key role in initiation and progression of atherosclerosis. However, little is known about the influence of various types of exercise training on LDL subfraction profile in athletes atthe beginning of professional career. Method: The study was performed in the group of young males: 37 rowers (at age 14,4±1,1 years) and 29 football players(14,7±2,1 years) within 3-month sport-specific training varying in exercise loads (IIIC vs IC according to Mitchell’s classification respectively).Blood lipid profile with LDL according to Friedewald’s formula and proportion of HDL, VLDL and LDL subfractions were assessed respectively by spectrophotometry (Pentra 400 Horiba) and electrophoresis methods (Lipoprint Quantimetrix). Results: Total LDL significantly increased in both groups: 63,1±18,3 mg% vs. 72,3±23,9 p<0,001 (rowers) and 70,1±15,9 mg% vs.81,1±14,7 mg% p<0,005 (football players). TC/HDL ratio increased only in rowers: 2,6±0,5vs. 2,8±0,6 p<0,005. Significant shifts in proportions of lipoprotein fractions differed in both groups by electrophoresis. Although more pronounced changes were related to LDL subfractions in football players, the number ofathletes with more atherogenic subfractions (LDL-3 and LDL-4) increased almost twice in rowers (table).