Integrin α(IIb)β₃ exists in an activated state in subjects with elevated plasma homocysteine levels.

Hdl Handle:
http://hdl.handle.net/10147/253613
Title:
Integrin α(IIb)β₃ exists in an activated state in subjects with elevated plasma homocysteine levels.
Authors:
McGarrigle, Sarah A; O'Neill, Sarah; Walsh, Geraldine M; Moran, Niamh; Graham, Ian M; Cooney, Marie-Therese; Monavari, Ahmad; Mayne, Philip; Collins, Patrick
Affiliation:
Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin, Ireland.
Citation:
Integrin α(IIb)β₃ exists in an activated state in subjects with elevated plasma homocysteine levels. 2011, 22 (1):65-73 Platelets
Publisher:
Platelets
Journal:
Platelets
Issue Date:
2011
URI:
http://hdl.handle.net/10147/253613
DOI:
10.3109/09537104.2010.512646
PubMed ID:
21133649
Abstract:
Elevated levels of plasma homocysteine (Hcy) are an independent risk factor for cardiovascular disease and thrombosis. The molecular basis for this phenomenon is not known but may relate to modification of cell surface thiols. The platelet specific integrin α(IIb)β₃ is a cysteine-rich cell adhesion molecule that plays a critical role in platelet aggregation and adhesion in haemostasis and thrombosis. In this study, we looked for evidence of a homocysteine-induced modification of α(IIb)β₃ using a fluorescently labeled PAC-1 antibody that recognizes the activated conformation of the integrin on the platelet surface. We show that exogenous Hcy (10-100 µM) and homocysteine thiolactone (HcyTL) (10-100 µM) increased PAC-1 binding to platelets in a concentration dependent manner in vitro. In parallel, we show subjects with clinical hyperhomocysteinemia exhibit a greater degree of activation of α(IIb)β₃ compared to age-matched controls. These findings demonstrate that circulating Hcy can modulate the activation state of the platelet integrin α(IIb)β₃, a key player in platelet aggregation and thrombosis.
Item Type:
Article
Language:
en
MeSH:
Antibodies; Binding Sites, Antibody; Blood Platelets; Case-Control Studies; Female; Homocysteine; Humans; Hyperhomocysteinemia; Integrins; Male; Platelet Activation; Platelet Aggregation; Platelet Glycoprotein GPIIb-IIIa Complex; Protein Binding; Risk Factors; Sulfhydryl Compounds; Thrombosis
ISSN:
1369-1635

Full metadata record

DC FieldValue Language
dc.contributor.authorMcGarrigle, Sarah Aen_GB
dc.contributor.authorO'Neill, Sarahen_GB
dc.contributor.authorWalsh, Geraldine Men_GB
dc.contributor.authorMoran, Niamhen_GB
dc.contributor.authorGraham, Ian Men_GB
dc.contributor.authorCooney, Marie-Thereseen_GB
dc.contributor.authorMonavari, Ahmaden_GB
dc.contributor.authorMayne, Philipen_GB
dc.contributor.authorCollins, Patricken_GB
dc.date.accessioned2012-11-28T09:58:37Z-
dc.date.available2012-11-28T09:58:37Z-
dc.date.issued2011-
dc.identifier.citationIntegrin α(IIb)β₃ exists in an activated state in subjects with elevated plasma homocysteine levels. 2011, 22 (1):65-73 Plateletsen_GB
dc.identifier.issn1369-1635-
dc.identifier.pmid21133649-
dc.identifier.doi10.3109/09537104.2010.512646-
dc.identifier.urihttp://hdl.handle.net/10147/253613-
dc.description.abstractElevated levels of plasma homocysteine (Hcy) are an independent risk factor for cardiovascular disease and thrombosis. The molecular basis for this phenomenon is not known but may relate to modification of cell surface thiols. The platelet specific integrin α(IIb)β₃ is a cysteine-rich cell adhesion molecule that plays a critical role in platelet aggregation and adhesion in haemostasis and thrombosis. In this study, we looked for evidence of a homocysteine-induced modification of α(IIb)β₃ using a fluorescently labeled PAC-1 antibody that recognizes the activated conformation of the integrin on the platelet surface. We show that exogenous Hcy (10-100 µM) and homocysteine thiolactone (HcyTL) (10-100 µM) increased PAC-1 binding to platelets in a concentration dependent manner in vitro. In parallel, we show subjects with clinical hyperhomocysteinemia exhibit a greater degree of activation of α(IIb)β₃ compared to age-matched controls. These findings demonstrate that circulating Hcy can modulate the activation state of the platelet integrin α(IIb)β₃, a key player in platelet aggregation and thrombosis.en_GB
dc.language.isoenen
dc.publisherPlateletsen_GB
dc.rightsArchived with thanks to Plateletsen_GB
dc.subject.meshAntibodies-
dc.subject.meshBinding Sites, Antibody-
dc.subject.meshBlood Platelets-
dc.subject.meshCase-Control Studies-
dc.subject.meshFemale-
dc.subject.meshHomocysteine-
dc.subject.meshHumans-
dc.subject.meshHyperhomocysteinemia-
dc.subject.meshIntegrins-
dc.subject.meshMale-
dc.subject.meshPlatelet Activation-
dc.subject.meshPlatelet Aggregation-
dc.subject.meshPlatelet Glycoprotein GPIIb-IIIa Complex-
dc.subject.meshProtein Binding-
dc.subject.meshRisk Factors-
dc.subject.meshSulfhydryl Compounds-
dc.subject.meshThrombosis-
dc.titleIntegrin α(IIb)β₃ exists in an activated state in subjects with elevated plasma homocysteine levels.en_GB
dc.typeArticleen
dc.contributor.departmentMolecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin, Ireland.en_GB
dc.identifier.journalPlateletsen_GB
dc.description.provinceLeinsteren

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