title: Decreased levels of platelet-derived soluble glycoprotein VI detected prior to the first diagnosis of coronary artery disease in HIV-positive individuals.
abstract: HIV-positive patients are at increased risk for coronary artery disease (CAD); changes in platelet activation may play a role. This study was performed to determine if levels of soluble glycoprotein VI (sGPVI), a platelet-specific marker of activation, were different in HIV-positive patients compared with HIV-negative controls and further if levels were predictive of CAD in HIV. Twenty-four HIV-positive individuals (HIV cases) with CAD were compared with 46 age- and sex-matched HIV-positive controls without CAD and 41 HIV-negative controls (healthy controls). Platelet activation (represented by sGPVI level) was compared 12 months and 1 month prior to CAD diagnosis. sGPVI was quantified by ELISA. sGPVI levels were higher in HIV-positive subjects (combined) than healthy controls (122.5 ng/mL [interquartile ranges (IQR) 90.3-160.5] versus 84.7 ng/mL [IQR 48.6-119.5], p <0.001). Twelve months before the event, there was no difference in sGPVI between HIV cases and HIV controls (113.4 ng/mL [IQR 85.6-141.65] versus 128.0 ng/mL [IQR 96.6-179.4], p = 0.369). One month prior to the event, sGPVI was significantly lower in HIV cases compared with HIV controls (109.0 ng/mL [IQR 79.4-123.4] versus 133.9 ng/mL [IQR 112.7-171.9], p = 0.010). These results remained significant following adjustment for possible confounders. This work demonstrates that HIV infection is associated with higher sGPVI levels. A fall in sGPVI immediately prior to first coronary artery event may reflect a loss of negative-feedback mechanism and be an important pathological step in the development of symptomatic CAD, but further work is needed to confirm these findings and determine their clinical impact.
authors.affiliation: a Department of Infectious Diseases , The Alfred Hospital and Monash University , Melbourne , Australia.
authors.forename: J M
authors.initials: JM
authors.lastname: Trevillyan
authors.affiliation: b Department of Cancer Biology and Therapeutics , Australian National University , Canberra , Australia.
authors.forename: E E
authors.initials: EE
authors.lastname: Gardiner
authors.affiliation: c Australian Centre for Blood Diseases , Monash University , Melbourne , Australia.
authors.forename: R K
authors.initials: RK
authors.lastname: Andrews
authors.affiliation: d Centre for Biomedical Research , Burnet Institute , Melbourne , Australia.
authors.forename: A
authors.initials: A
authors.lastname: Maisa
authors.affiliation: a Department of Infectious Diseases , The Alfred Hospital and Monash University , Melbourne , Australia.|d Centre for Biomedical Research , Burnet Institute , Melbourne , Australia.
authors.forename: A C
authors.initials: AC
authors.lastname: Hearps
authors.affiliation: e Immunology Section, Basic Medical Sciences Department, Faculty of Medicine , Hashemite University , Zarqa , Jordan.
authors.forename: M
authors.initials: M
authors.lastname: Al-Tamimi
authors.affiliation: a Department of Infectious Diseases , The Alfred Hospital and Monash University , Melbourne , Australia.|d Centre for Biomedical Research , Burnet Institute , Melbourne , Australia.
authors.forename: S M
authors.initials: SM
authors.lastname: Crowe
authors.affiliation: a Department of Infectious Diseases , The Alfred Hospital and Monash University , Melbourne , Australia.
authors.forename: J F
authors.initials: JF
authors.lastname: Hoy
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D001792:Blood Platelets / Q000378:metabolism* / Q000821:virology; D016022:Case-Control Studies; D003324:Coronary Artery Disease / Q000097:blood / Q000150:complications / Q000175:diagnosis* / Q000821:virology; D005260:Female; D015658:HIV Infections / Q000097:blood* / Q000150:complications / Q000821:virology; D006801:Humans; D008297:Male; D008875:Middle Aged; D015539:Platelet Activation; D010976:Platelet Count; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D010980:Platelet Membrane Glycoproteins; C098341:platelet membrane glycoprotein VI
keywords: Cardiovascular disease; HIV; Thrombosis; soluble glycoprotein VI