title: Young women with polycystic ovary syndrome have raised levels of circulating annexin V-positive platelet microparticles.
abstract: OBJECTIVE
  Are circulating microparticles (MPs) altered in young women with polycystic ovary syndrome (PCOS)?
  
  
  CONCLUSIONS
  Women with PCOS have elevated concentrations of circulating platelet-derived MPs, which exhibit increased annexin V binding and altered microRNA (miR) profiles compared with healthy volunteers.
  
  
  BACKGROUND
  Some studies have shown that cardiovascular risk is increased in young women with PCOS but the mechanisms by which this occurs are uncertain. Circulating MPs are elevated in patients with cardiovascular disease but the characteristics of MPs in patients with PCOS are unclear.
  
  
  METHODS
  Case-control study comprising 17 women with PCOS (mean ± SD; age 31 ± 7 years, BMI 29 ± 6 kg/m(2)) and 18 healthy volunteers (age 31 ± 6 years, BMI 30 ± 6 kg/m(2)).
  
  
  METHODS
  The study was conducted in a University hospital. Nanoparticle tracking analysis (NTA) and flow cytometry (CD41 platelet, CD11b monocyte, CD144 endothelial) were used to determine MP size, concentration, cellular origin and annexin V positivity (reflecting phosphatidylserine exposure). Fatty acid analysis was performed by gas chromatography and MP miR expression profiles were compared by microarray.
  
  
  RESULTS
  PCOS subjects showed increased MP concentrations compared with healthy volunteers (mean ± SD; 11.5 ± 5 × 10(12)/ml versus 10.0 ± 4 × 10(12)/ml, respectively; P = 0.03), which correlated with the homeostasis model of insulin resistance (r = 0.53, P = 0.03). This difference was predominantly seen in MPs whose size was in the small exosomal range (<150 nm in diameter, P< 0.05). PCOS patients showed a greater percentage of annexin V(+) MPs compared with healthy volunteers (84 ± 18 versus 74 ± 24%, respectively, P = 0.05) but the cellular origin of MPs, which were predominantly platelet-derived (PCOS: 99 ± 0.9%; controls: 99 ± 2.5%), did not differ. MP fatty acid concentration and composition was similar between groups but 16 miRs were differentially expressed (P < 0.05).
  
  
  CONCLUSIONS
  Patients with PCOS were classified by the Rotterdam criteria, which describes a less severe metabolic phenotype than other definitions of the syndrome. Our findings may thus not be generalizable to all patients with PCOS. MicroRNA expression analysis was only undertaken in an exploratory subset of the overall study population hence, validation of our findings in a larger cohort is mandatory. Furthermore, miR levels were unaltered for the highly expressed miRs and it is unclear whether differences in the lowly expressed miRs carries pathological relevance.
  
  
  CONCLUSIONS
  This study suggests that women with PCOS have an altered MP profile but further studies are needed to confirm this, to explore the mechanisms by which these alterations develop and to establish whether therapies that improve insulin sensitivity are able to reduce circulating MP concentrations.
  
  
  BACKGROUND
  The study was funded by grants from the Wales Heart Research Institute and Mrs John Nixon Scholarship. The authors have no conflicts of interest to declare.
authors.affiliation: Institute of Molecular and Experimental Medicine, Cardiff University, Cardiff CF14 4XN, UK.
authors.forename: G R
authors.initials: GR
authors.lastname: Willis
authors.affiliation: Institute of Molecular and Experimental Medicine, Cardiff University, Cardiff CF14 4XN, UK.
authors.forename: K
authors.initials: K
authors.lastname: Connolly
authors.affiliation: Institute of Infection and Immunity, Cardiff University, Cardiff CF14 4XN, UK.
authors.forename: K
authors.initials: K
authors.lastname: Ladell
authors.affiliation: School of Biosciences, Cardiff University, Cardiff CF10 3AX, UK.
authors.forename: T S
authors.initials: TS
authors.lastname: Davies
authors.affiliation: School of Biosciences, Cardiff University, Cardiff CF10 3AX, UK.
authors.forename: I A
authors.initials: IA
authors.lastname: Guschina
authors.affiliation: School of Biosciences, Cardiff University, Cardiff CF10 3AX, UK.
authors.forename: D
authors.initials: D
authors.lastname: Ramji
authors.affiliation: Institute of Infection and Immunity, Cardiff University, Cardiff CF14 4XN, UK.
authors.forename: K
authors.initials: K
authors.lastname: Miners
authors.affiliation: Institute of Infection and Immunity, Cardiff University, Cardiff CF14 4XN, UK.
authors.forename: D A
authors.initials: DA
authors.lastname: Price
authors.affiliation: Institute of Cancer and Genetics, Cardiff University, Velindre Cancer Centre, Whitchurch, Cardiff CF14 2TL, UK.
authors.forename: A
authors.initials: A
authors.lastname: Clayton
authors.affiliation: Institute of Molecular and Experimental Medicine, Cardiff University, Cardiff CF14 4XN, UK.
authors.forename: P E
authors.initials: PE
authors.lastname: James
authors.affiliation: Institute of Molecular and Experimental Medicine, Cardiff University, Cardiff CF14 4XN, UK reesda@cf.ac.uk.
authors.forename: D A
authors.initials: DA
authors.lastname: Rees
mesh_terms: D000328:Adult; D017304:Annexin A5 / Q000097:blood*; D001792:Blood Platelets / Q000378:metabolism*; D016022:Case-Control Studies; D055252:Cell-Derived Microparticles / Q000378:metabolism; D005260:Female; D006801:Humans; D007333:Insulin Resistance; D011085:Polycystic Ovary Syndrome / Q000378:metabolism*; D012307:Risk Factors
chemical_list: D017304:Annexin A5
keywords: insulin resistance; microparticles; polycystic ovary syndrome