title: Microparticle-associated vascular adhesion molecule-1 and tissue factor follow a circadian rhythm in healthy human subjects.
abstract: An increased risk of death or severe injury due to late-morning thrombotic events is well established. Tissue factor (TF) is the initiator of the coagulation cascade, and endothelial stresses, coupled with production of pro-coagulant microparticles (MP) are also important factors in loss of haemostasis. TF and vascular cell adhesion molecule-1 (VCAM-1) -positive cell microparticles were assessed periodically over a 24-hour (h) period in healthy human subjects to ascertain if they followed a circadian rhythm. Eleven healthy male subjects were assessed in a temperature-controlled environment with dietary intake consistent between subjects. Blood samples were taken every 4 h by venipuncture, and TF and VCAM-1 positive microparticles were quantified by flow cytometry. A significant circadian rhythm was observed in VCAM-1 MP (p=or<0.0001), and a trend was shown, although not statistically significant (p=0.065) in TF microparticles. A peak was observed at 9 a.m. for VCAM-1 positive MP, followed by a decrease and subsequent peak at 9 p.m. and a minimum at 5 a.m. TF-positive MP followed a strikingly similar trend in both variation and absolute numbers with a delay. A circadian rhythm was observed in VCAM-1 and less so TF-positive MP. This has significant implications in terms of the well known increased risk of cardiovascular thrombotic events matching this data. To our knowledge this is the first such report of quantified measurements of these MP over a 24-h period and the only measurement of a 24-h variation of in-vivo blood-borne TF.
authors.affiliation: Medical Research Laboratory, Post-Graduate Medical Institute, Wolfson Building, University of Hull, Cottingham Road, Hull, HU6 7RX, UK. l.a.madden@hull.ac.uk
authors.forename: Leigh A
authors.initials: LA
authors.lastname: Madden
authors.forename: Rebecca V
authors.initials: RV
authors.lastname: Vince
authors.forename: Marie E
authors.initials: ME
authors.lastname: Sandström
authors.forename: Lee
authors.initials: L
authors.lastname: Taylor
authors.forename: Lars
authors.initials: L
authors.lastname: McNaughton
authors.forename: Gerard
authors.initials: G
authors.lastname: Laden
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000097:blood / Q000503:physiopathology; D021961:Cell Membrane Structures / Q000378:metabolism*; D002940:Circadian Rhythm; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D012016:Reference Values; D013925:Thromboplastin / Q000378:metabolism*; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood*
chemical_list: D015415:Biomarkers; D019010:Vascular Cell Adhesion Molecule-1; D013925:Thromboplastin