Purpose: Hormonal status and menopause affect human macrophage function and cardiometabolic risk. In polycystic ovary syndrome (PCOS) patients the cardiometabolic risk increases through mechanisms that are largely unknown. We tested the hypotheses that macrophage activation is influenced by menstrual cycle and that ovarian dysfunction in PCOS patients is associated with altered macrophage inflammatory responses and cholesterol efflux capacity of serum HDL. Methods: Blood samples were obtained in the follicular and luteal phases from cycling women (n = 10) and on a single visit from PCOS patients with ovarian dysfunction (n = 11). Monocyte-derived macrophage activation and monocyte subsets were characterized ex vivo using flow cytometry. The capacity of HDL to promote cell cholesterol efflux through the main efflux pathways, namely aqueous diffusion, ATP-binding cassette A1 and G1, was also evaluated. Results: Hormone and metabolic profiles differed as expected in relation to menstrual cycle and ovulatory dysfunction. Overall, macrophage responses to activating stimuli in PCOS patients were blunted compared with cycling women. Macrophages in the follicular phase were endowed with enhanced responsiveness to LPS/interferon-γ compared with the luteal phase and PCOS. These changes were not related to baseline differences in monocytes. HDL cholesterol efflux capacity through multiple pathways was significantly impaired in PCOS patients compared to healthy women, at least in part independent from lower HDL-cholesterol levels. Conclusions: Regular menstrual cycles entailed fluctuations in macrophage activation. Such dynamic pattern was attenuated in PCOS. Along with impaired HDL function, this may contribute to the increased cardiometabolic risk associated with PCOS.
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