Integrin α(IIb)β₃ exists in an activated state in subjects with elevated plasma homocysteine levels.
Authors
McGarrigle, Sarah AO'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.Issue Date
2011MeSH
AntibodiesBinding 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
Metadata
Show full item recordCitation
Integrin α(IIb)β₃ exists in an activated state in subjects with elevated plasma homocysteine levels. 2011, 22 (1):65-73 PlateletsPublisher
PlateletsJournal
PlateletsDOI
10.3109/09537104.2010.512646PubMed ID
21133649Abstract
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
ArticleLanguage
enISSN
1369-1635ae974a485f413a2113503eed53cd6c53
10.3109/09537104.2010.512646
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