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Haptoglobin inhibits phospholipid transfer protein activity in hyperlipidemic human plasma

BACKGROUND: Haptoglobin is a plasma protein that scavenges haemoglobin during haemolysis. Phospholipid Transfer Protein (PLTP) transfers lipids from Low Density Lipoproteins (LDL) to High Density Lipoproteins (HDL). PLTP is involved in the pathogenesis of atherosclerosis which causes coronary artery...

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Autores principales: Henderson, Ryan J, Wasan, Kishor M, Leon, Carlos G
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2729738/
https://www.ncbi.nlm.nih.gov/pubmed/19627602
http://dx.doi.org/10.1186/1476-511X-8-27
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author Henderson, Ryan J
Wasan, Kishor M
Leon, Carlos G
author_facet Henderson, Ryan J
Wasan, Kishor M
Leon, Carlos G
author_sort Henderson, Ryan J
collection PubMed
description BACKGROUND: Haptoglobin is a plasma protein that scavenges haemoglobin during haemolysis. Phospholipid Transfer Protein (PLTP) transfers lipids from Low Density Lipoproteins (LDL) to High Density Lipoproteins (HDL). PLTP is involved in the pathogenesis of atherosclerosis which causes coronary artery disease, the leading cause of death in North America. It has been shown that Apolipoprotein-A1 (Apo-A1) binds and regulates PLTP activity. Haptoglobin can also bind to Apo-A1, affecting the ability of Apo-A1 to induce enzymatic activities. Thus we hypothesize that haptoglobin inhibits PLTP activity. This work tested the effect of Haptoglobin and Apo-A1 addition on PLTP activity in human plasma samples. The results will contribute to our understanding of the role of haptoglobin on modulating reverse cholesterol transport. RESULTS: We analyzed the PLTP activity and Apo-A1 and Haptoglobin content in six hyperlipidemic and six normolipidemic plasmas. We found that Apo-A1 levels are proportional to PLTP activity in hyperlipidemic (R(2 )= 0.66, p < 0.05) but not in normolipidemic human plasma. Haptoglobin levels and PLTP activity are inversely proportional in hyperlipidemic plasmas (R(2 )= 0.57, p > 0.05). When the PLTP activity was graphed versus the Hp/Apo-A1 ratio in hyperlipidemic plasma there was a significant correlation (R(2 )= 0.69, p < 0.05) suggesting that PLTP activity is affected by the combined effect of Apo-A1 and haptoglobin. When haptoglobin was added to individual hyperlipidemic plasma samples there was a dose dependent decrease in PLTP activity. In these samples we also found a negative correlation (-0.59, p < 0.05) between PLTP activity and Hp/Apo-A1. When we added an amount of haptoglobin equivalent to 100% of the basal levels, we found a 64 ± 23% decrease (p < 0.05) in PLTP activity compared to basal PLTP activity. We tested the hypothesis that additional Apo-A1 would induce PLTP activity. Interestingly we found a dose dependent decrease in PLTP activity upon Apo-A1 addition. When both Apo-A1 and Hpt were added to the plasma samples there was no further reduction in PLTP activity suggesting that they act through a common pathway. CONCLUSION: These findings suggest an inhibitory effect of Haptoglobin over PLTP activity in hyperlipidemic plasma that may contribute to the regulation of reverse cholesterol transport.
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spelling pubmed-27297382009-08-21 Haptoglobin inhibits phospholipid transfer protein activity in hyperlipidemic human plasma Henderson, Ryan J Wasan, Kishor M Leon, Carlos G Lipids Health Dis Research BACKGROUND: Haptoglobin is a plasma protein that scavenges haemoglobin during haemolysis. Phospholipid Transfer Protein (PLTP) transfers lipids from Low Density Lipoproteins (LDL) to High Density Lipoproteins (HDL). PLTP is involved in the pathogenesis of atherosclerosis which causes coronary artery disease, the leading cause of death in North America. It has been shown that Apolipoprotein-A1 (Apo-A1) binds and regulates PLTP activity. Haptoglobin can also bind to Apo-A1, affecting the ability of Apo-A1 to induce enzymatic activities. Thus we hypothesize that haptoglobin inhibits PLTP activity. This work tested the effect of Haptoglobin and Apo-A1 addition on PLTP activity in human plasma samples. The results will contribute to our understanding of the role of haptoglobin on modulating reverse cholesterol transport. RESULTS: We analyzed the PLTP activity and Apo-A1 and Haptoglobin content in six hyperlipidemic and six normolipidemic plasmas. We found that Apo-A1 levels are proportional to PLTP activity in hyperlipidemic (R(2 )= 0.66, p < 0.05) but not in normolipidemic human plasma. Haptoglobin levels and PLTP activity are inversely proportional in hyperlipidemic plasmas (R(2 )= 0.57, p > 0.05). When the PLTP activity was graphed versus the Hp/Apo-A1 ratio in hyperlipidemic plasma there was a significant correlation (R(2 )= 0.69, p < 0.05) suggesting that PLTP activity is affected by the combined effect of Apo-A1 and haptoglobin. When haptoglobin was added to individual hyperlipidemic plasma samples there was a dose dependent decrease in PLTP activity. In these samples we also found a negative correlation (-0.59, p < 0.05) between PLTP activity and Hp/Apo-A1. When we added an amount of haptoglobin equivalent to 100% of the basal levels, we found a 64 ± 23% decrease (p < 0.05) in PLTP activity compared to basal PLTP activity. We tested the hypothesis that additional Apo-A1 would induce PLTP activity. Interestingly we found a dose dependent decrease in PLTP activity upon Apo-A1 addition. When both Apo-A1 and Hpt were added to the plasma samples there was no further reduction in PLTP activity suggesting that they act through a common pathway. CONCLUSION: These findings suggest an inhibitory effect of Haptoglobin over PLTP activity in hyperlipidemic plasma that may contribute to the regulation of reverse cholesterol transport. BioMed Central 2009-07-23 /pmc/articles/PMC2729738/ /pubmed/19627602 http://dx.doi.org/10.1186/1476-511X-8-27 Text en Copyright © 2009 Henderson et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Henderson, Ryan J
Wasan, Kishor M
Leon, Carlos G
Haptoglobin inhibits phospholipid transfer protein activity in hyperlipidemic human plasma
title Haptoglobin inhibits phospholipid transfer protein activity in hyperlipidemic human plasma
title_full Haptoglobin inhibits phospholipid transfer protein activity in hyperlipidemic human plasma
title_fullStr Haptoglobin inhibits phospholipid transfer protein activity in hyperlipidemic human plasma
title_full_unstemmed Haptoglobin inhibits phospholipid transfer protein activity in hyperlipidemic human plasma
title_short Haptoglobin inhibits phospholipid transfer protein activity in hyperlipidemic human plasma
title_sort haptoglobin inhibits phospholipid transfer protein activity in hyperlipidemic human plasma
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2729738/
https://www.ncbi.nlm.nih.gov/pubmed/19627602
http://dx.doi.org/10.1186/1476-511X-8-27
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