Autophagy and mitophagy in circulating immune cells of women with polycystic ovary syndrome: A cardiovascular perspective.

INTRODUCTION

Polycystic ovary syndrome (PCOS) is a complex endocrine disorder associated with systemic inflammation, oxidative stress, and increased cardiometabolic risk. While impaired autophagy and mitophagy have been implicated in tissue-specific dysfunction, their role in circulating immune cells and relation to early vascular alterations remain unclear.

METHODS

In this cross-sectional study, 91 women (48 controls, 43 with PCOS) underwent anthropometric and biochemical assessment. Systemic markers included myeloperoxidase (MPO), glutathione, TNFα, and sP-selectin were determined in serum. Superoxide production (dHE), mitochondrial membrane potential (TMRM), and protein levels of BECLIN1, LC3II/I, P62, NBR1, and PINK1 were assessed in peripheral blood mononuclear cells (PBMCs). Neutrophil-endothelial cell interactions were analysed as subclinical markers of endothelial dysfunction.

RESULTS

PCOS patients presented hormonal, lipid, and glucose abnormalities, accompanied by redox imbalance, elevated MPO and superoxide levels, reduced glutathione, and increased mitochondrial membrane potential. Autophagy and mitophagy pathways were significantly impaired in PBMCs, and the expression of all assessed markers was reduced. These alterations were associated with androgen excess, oxidative stress, and inflammation. Elevated sP-selectin and enhanced neutrophil-endothelial interactions indicated early endothelial dysfunction in PCOS women.

CONCLUSION

Our findings reveal that women with PCOS display autophagy and mitophagy impairment in immune cells, processes that are linked to oxidative and inflammatory stress and accompanied by endothelial alterations, highlighting a potential mechanistic pathway contributing to their cardiometabolic risk.