Wilfried Schgoer1, Thomas Mueller2, Matti Jauhiainen3, Andreas Wehinger4, Roland Gander1, Ivan Tancevski1, Karin Salzmann1, Philipp Eller1, Andreas Ritsch1, Meinhard Haltmayer2, Christian Ehnholm3, Josef R Patsch1, Bernhard Foeger5. 1. Department of Internal Medicine, Medical University Innsbruck, Austria. 2. Department of Laboratory Medicine, Konventhospital Barmherzige Brueder, Linz, Austria. 3. Department of Molecular Medicine, National Public Health Institute, Biomedicum, Helsinki, Finland. 4. Department of Internal Medicine, Medical University Innsbruck, Austria; Department of Internal Medicine, Landeskrankenhaus Bregenz, Austria. 5. Department of Internal Medicine, Medical University Innsbruck, Austria; Department of Internal Medicine, Landeskrankenhaus Bregenz, Austria. Electronic address: bernhard.foeger@lkhb.at.
Abstract
OBJECTIVE: Phospholipid transfer protein (PLTP) facilitates cholesterol efflux from cells, intravascular HDL remodelling and transfer of vitamin E and endotoxin. In humans, the relationship of PLTP to atherosclerosis is unknown. However, strong coronary risk factors like obesity, diabetes, cigarette smoking and inflammation increase circulating levels of active PLTP. The aim of the present, cross-sectional study was to analyze the relationship of PLTP to peripheral arterial disease, a marker of generalized atherosclerosis, independently of potentially confounding factors like obesity, diabetes and smoking. METHODS: We performed a case control study in 153 patients with symptomatic peripheral arterial disease (PAD) and 208 controls free of vascular disease. Smokers and patients with diabetes mellitus were excluded. A lipoprotein-independent assay was used for measurement of circulating bioactive PLTP and an ELISA utilizing a monoclonal antibody was used to analyze PLTP mass. RESULTS: PLTP activity was significantly decreased in patients with PAD 5.5 (4.6-6.4)(median (25th-75th percentile)) versus 5.9 (5.1-6.9) micromol/mL/h in controls (p=0.001). In contrast, PLTP mass was similar in patients with PAD 8.5 microg/mL (7.3-9.5) and in controls 8.3 microg/mL (6.9-9.7) (p=0.665). Multivariate logistic regression analysis revealed that PLTP activity is independently associated with the presence of PAD. PLTP activity was similar in patients with and without lipid-lowering drugs (p=0.396). CONCLUSION: Our results show that in non-diabetic, non-smoking subjects low rather than high PLTP activity is a marker for the presence of peripheral arterial disease and that distribution of PLTP between high-activity and low-activity forms may be compromised in atherosclerosis.
OBJECTIVE:Phospholipid transfer protein (PLTP) facilitates cholesterol efflux from cells, intravascular HDL remodelling and transfer of vitamin E and endotoxin. In humans, the relationship of PLTP to atherosclerosis is unknown. However, strong coronary risk factors like obesity, diabetes, cigarette smoking and inflammation increase circulating levels of active PLTP. The aim of the present, cross-sectional study was to analyze the relationship of PLTP to peripheral arterial disease, a marker of generalized atherosclerosis, independently of potentially confounding factors like obesity, diabetes and smoking. METHODS: We performed a case control study in 153 patients with symptomatic peripheral arterial disease (PAD) and 208 controls free of vascular disease. Smokers and patients with diabetes mellitus were excluded. A lipoprotein-independent assay was used for measurement of circulating bioactive PLTP and an ELISA utilizing a monoclonal antibody was used to analyze PLTP mass. RESULTS:PLTP activity was significantly decreased in patients with PAD 5.5 (4.6-6.4)(median (25th-75th percentile)) versus 5.9 (5.1-6.9) micromol/mL/h in controls (p=0.001). In contrast, PLTP mass was similar in patients with PAD 8.5 microg/mL (7.3-9.5) and in controls 8.3 microg/mL (6.9-9.7) (p=0.665). Multivariate logistic regression analysis revealed that PLTP activity is independently associated with the presence of PAD. PLTP activity was similar in patients with and without lipid-lowering drugs (p=0.396). CONCLUSION: Our results show that in non-diabetic, non-smoking subjects low rather than high PLTP activity is a marker for the presence of peripheral arterial disease and that distribution of PLTP between high-activity and low-activity forms may be compromised in atherosclerosis.
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