Plasminogen activator inhibitor-1 removal using dextran sulphate columns. Evidence of PAI-1 homeostasis.

Hdl Handle:
http://hdl.handle.net/10147/253675
Title:
Plasminogen activator inhibitor-1 removal using dextran sulphate columns. Evidence of PAI-1 homeostasis.
Authors:
Maher, Vincent M G; Kitano, Yuri; Neuwirth, Clare; Davies, Graham J; Maseri, Attilio; Thompson, Gilbert R; Andreotti, Felicita
Affiliation:
Department of Cardiology, Adelaide Meath Hospital, Dublin, Ireland. vmaher@gmail.com
Citation:
Plasminogen activator inhibitor-1 removal using dextran sulphate columns. Evidence of PAI-1 homeostasis. 2009, 28 (2):166-72 J. Thromb. Thrombolysis
Publisher:
Journal of thrombosis and thrombolysis
Journal:
Journal of thrombosis and thrombolysis
Issue Date:
Aug-2009
URI:
http://hdl.handle.net/10147/253675
DOI:
10.1007/s11239-008-0260-8
PubMed ID:
18665328
Abstract:
Patients with high plasma plasminogen activator inhibitor-1 (PAI-1) antigen levels are prone to develop thrombosis. Lowering PAI-1 levels may offer a therapeutic option and help to better understand PAI-1 metabolism. We examined the effect on plasma PAI-1 levels of LDL-apheresis using dextran sulphate (DS) columns in 12 patients (9 male, 3 female, 49 +/- 10 years) with heterozygous familial hypercholesterolaemia and coronary artery disease. One plasma volume equivalent (2.3-4.0 l) was treated during each procedure (at flow rates of 23 +/- 2 ml/min). Lipids and PAI-1 antigen levels were measured in plasma before and immediately after 19 aphereses (once in 7 patients, twice in 3 patients and three times in 2 patients) and also at 3 and 7 days post apheresis in five of these patients and in the column eluates from 8 of these patients. DS-apheresis reduced plasma cholesterol (50 +/- 8%), triglyceride (45 +/- 27%), apolipoprotein B (59 +/- 10%) and PAI-1 antigen levels from 10.2 +/- 5.2 to 6.0 +/- 3.1 ng/ml (P = 0.005). The PAI-I changes were independent of circadian variation. PAI-I bound to the DS-columns (3.51 +/- 1.03 ng/ml filtered plasma) and the percent of filtered PAI-1 that was bound correlated inversely (r = -0.81, P < 0.02) with basal PAI-1 levels indicating a high affinity saturable binding process. In four patients, plasma PAI-1 levels post-apheresis were higher than expected based on the amount of PAI-removed by the DS columns. The difference between the expected and actual PAI-1 level post apheresis, reflecting PAI-1 secretion or extracellular redistribution, correlated inversely with basal PAI-1 levels (r = -0.83, P = 0.01). PAI-1 levels returned to baseline pre-apheresis values 7 days post apheresis. PAI-1 antigen may be removed from plasma without adverse effect, resulting temporarily in its extracellular redistribution and restoration to baseline levels over one week. PAI-1 redistribution particularly when baseline pre-apheresis values were low may reflect a homeostatic mechanism to maintain sufficient PAI-1 levels. Procedures that could selectively remove PAI-1 from plasma may offer a treatment option for those with very high plasma PAI-1 levels and thrombosis.
Item Type:
Article
Language:
en
MeSH:
Adult; Blood Component Removal; Cholesterol, LDL; Coronary Artery Disease; Dextran Sulfate; Female; Homeostasis; Humans; Hyperlipoproteinemia Type II; Male; Middle Aged; Plasminogen Activator Inhibitor 1
ISSN:
1573-742X

Full metadata record

DC FieldValue Language
dc.contributor.authorMaher, Vincent M Gen_GB
dc.contributor.authorKitano, Yurien_GB
dc.contributor.authorNeuwirth, Clareen_GB
dc.contributor.authorDavies, Graham Jen_GB
dc.contributor.authorMaseri, Attilioen_GB
dc.contributor.authorThompson, Gilbert Ren_GB
dc.contributor.authorAndreotti, Felicitaen_GB
dc.date.accessioned2012-11-28T12:33:58Z-
dc.date.available2012-11-28T12:33:58Z-
dc.date.issued2009-08-
dc.identifier.citationPlasminogen activator inhibitor-1 removal using dextran sulphate columns. Evidence of PAI-1 homeostasis. 2009, 28 (2):166-72 J. Thromb. Thrombolysisen_GB
dc.identifier.issn1573-742X-
dc.identifier.pmid18665328-
dc.identifier.doi10.1007/s11239-008-0260-8-
dc.identifier.urihttp://hdl.handle.net/10147/253675-
dc.description.abstractPatients with high plasma plasminogen activator inhibitor-1 (PAI-1) antigen levels are prone to develop thrombosis. Lowering PAI-1 levels may offer a therapeutic option and help to better understand PAI-1 metabolism. We examined the effect on plasma PAI-1 levels of LDL-apheresis using dextran sulphate (DS) columns in 12 patients (9 male, 3 female, 49 +/- 10 years) with heterozygous familial hypercholesterolaemia and coronary artery disease. One plasma volume equivalent (2.3-4.0 l) was treated during each procedure (at flow rates of 23 +/- 2 ml/min). Lipids and PAI-1 antigen levels were measured in plasma before and immediately after 19 aphereses (once in 7 patients, twice in 3 patients and three times in 2 patients) and also at 3 and 7 days post apheresis in five of these patients and in the column eluates from 8 of these patients. DS-apheresis reduced plasma cholesterol (50 +/- 8%), triglyceride (45 +/- 27%), apolipoprotein B (59 +/- 10%) and PAI-1 antigen levels from 10.2 +/- 5.2 to 6.0 +/- 3.1 ng/ml (P = 0.005). The PAI-I changes were independent of circadian variation. PAI-I bound to the DS-columns (3.51 +/- 1.03 ng/ml filtered plasma) and the percent of filtered PAI-1 that was bound correlated inversely (r = -0.81, P < 0.02) with basal PAI-1 levels indicating a high affinity saturable binding process. In four patients, plasma PAI-1 levels post-apheresis were higher than expected based on the amount of PAI-removed by the DS columns. The difference between the expected and actual PAI-1 level post apheresis, reflecting PAI-1 secretion or extracellular redistribution, correlated inversely with basal PAI-1 levels (r = -0.83, P = 0.01). PAI-1 levels returned to baseline pre-apheresis values 7 days post apheresis. PAI-1 antigen may be removed from plasma without adverse effect, resulting temporarily in its extracellular redistribution and restoration to baseline levels over one week. PAI-1 redistribution particularly when baseline pre-apheresis values were low may reflect a homeostatic mechanism to maintain sufficient PAI-1 levels. Procedures that could selectively remove PAI-1 from plasma may offer a treatment option for those with very high plasma PAI-1 levels and thrombosis.en_GB
dc.language.isoenen
dc.publisherJournal of thrombosis and thrombolysisen_GB
dc.rightsArchived with thanks to Journal of thrombosis and thrombolysisen_GB
dc.subject.meshAdult-
dc.subject.meshBlood Component Removal-
dc.subject.meshCholesterol, LDL-
dc.subject.meshCoronary Artery Disease-
dc.subject.meshDextran Sulfate-
dc.subject.meshFemale-
dc.subject.meshHomeostasis-
dc.subject.meshHumans-
dc.subject.meshHyperlipoproteinemia Type II-
dc.subject.meshMale-
dc.subject.meshMiddle Aged-
dc.subject.meshPlasminogen Activator Inhibitor 1-
dc.titlePlasminogen activator inhibitor-1 removal using dextran sulphate columns. Evidence of PAI-1 homeostasis.en_GB
dc.typeArticleen
dc.contributor.departmentDepartment of Cardiology, Adelaide Meath Hospital, Dublin, Ireland. vmaher@gmail.comen_GB
dc.identifier.journalJournal of thrombosis and thrombolysisen_GB
dc.description.provinceLeinsteren

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