Abstract
Are circulating microparticles (MPs) altered in young women with polycystic ovary syndrome (PCOS)? 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. 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. 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)). 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. 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). 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. 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. 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.
Highlights
Polycystic ovary syndrome (PCOS) is a common endocrine condition characterised by hyperandrogenism, polycystic ovaries and oligo/anovulation
What is known already: Some studies have shown that cardiovascular risk is increased in young women with polycystic ovary syndrome (PCOS) but the mechanisms by which this occurs is uncertain
MPs are elevated in patients with cardiovascular disease but the characteristics of MPs in patients with PCOS are unclear
Summary
Polycystic ovary syndrome (PCOS) is a common endocrine condition characterised by hyperandrogenism, polycystic ovaries and oligo/anovulation. In addition to its reproductive sequelae, PCOS is considered a metabolic disorder characterised by defects in insulin secretion and sensitivity (Ehrmann et al, 1995), which lead to an increased risk of type 2 diabetes (Morgan et al, 2012). Patients may be at increased risk of cardiovascular disease but the mechanisms by which these occur are not yet fully established. One process may involve endothelial dysfunction (El-Kannishy et al, 2010, Orio et al, 2004), an early marker of vascular disease which is associated with reduced nitric oxide (NO) bioavailability, increased oxidative stress and elevated circulating microparticles (MPs) (Amabile et al., 2005, Gündüz et al, 2012). Elevations in platelet-derived MPs (PMPs) have been observed in patients with coronary artery disease (CAD) (Koga et al, 2005, Mallat et al, 2000)
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