Activation profiles of monocyte-macrophages and HDL function in healthy women in relation to menstrual cycle and in polycystic ovary syndrome patients
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.
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.
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.
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.
KeywordsMacrophages Macrophage activation Cholesterol efflux Polycystic ovary syndrome Menstrual cycle Monocytes
We wish to thank Dr. Fabrizio Veglia for his valuable help in statistical analyses of HDL CEC data.
G.P.F., C.B., and A.C. conceived the idea and planned the experiments. R.M., M.B., S.P., C.S., and G.P.F. conducted the clinical part of the study, S.T. and R.C performed cell culture and flow cytometry analyses, S.T. and G.P.F. carried out statistical analysis, M.P.A., N.R., and F.B performed CEC and intracellular cholesterol assays and refined statistical analyses, M.P. was responsible for laboratory medicine data. A.C. wrote the draft and all authors made substantial contributions to the final manuscript.
This study was funded by institutional funding to M.P., C.B., C.S., F.B., G.P.F., and A.C.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
All procedures performed in studies involving human participants were in accordance with the ethical standards of Padova University Hospital Ethics Committee and with the 1964 Helsinki declaration and its later amendments.
Informed consent was obtained from all individual participants included in the study.
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