PhD Scientific Days 2025

Poster Session II. - J: Theoretical and Translational Medicine

The Role of HCN channels in the vascular adaptation to PCOS

Name of the presenter

Bányai Bálint

Institute/workplace of the presenter

Semmelweis University department of physiology

Authors

Bálint Bányai¹, Mária Szekeres², Ágnes Pakuts¹, Stella Kiss¹, Skyler Senuma Pang¹, Szabolcs Várbíró³, Rita Benkő¹, Eszter M. Horváth¹

1: Semmelweis University, Department of Physiology
2: Semmelweis University Faculty of Helath Sciences Department of Morphology and Physiology
3: University of Szeged Department of Obstetrics and Gyneacology

Text of the abstract

Polycystic ovary syndrome (PCOS) is a common endocrine disorder among women of reproductive age, The main symptom is hyperandrogenism, often associated with Vitamin D deficiency in approximately 80% of cases. Additionally, PCOS is linked to an increased cardiovascular risk. Previous studies have identified the presence of all four isotypes of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels in the thoracic aorta of rats, with ivabradine, a non-selective HCN inhibitor, exhibiting vasorelaxation effects. Altered HCN expression has also been observed in diabetes mellitus.
This study aimed to investigate changes in HCN-dependent vascular responses in a rat model of hyperandrogenism and evaluate the potential impact of Vitamin D supplementation.
A total of 44 female Wistar rats (weighing 70–90 g) were assigned to four experimental groups: control (C), Vitamin D-supplemented (D, 140 IU/100 g body weight), testosterone-treated (T, daily 3.3 mg/100 g transdermal Androgel), and a combination group receiving both Vitamin D and testosterone (T+D). After eight weeks, thoracic aortic segments were isolated to wire myography to assess ivabradine-induced relaxation following phenylephrine pre-contraction, and the remaining vessel segments after formalin fixed paraffin embedding going under immunohistochemical analysis against HCN1-4 .
Results demonstrated that Vitamin D supplementation marginally enhanced ivabradine-induced vasorelaxation (p=0,062). HCN1 expression was significantly elevated in the combined T+D group compared to the other three groups. HCN2 expression was elevated in testosterone-treated rats but this effect was mitigated by Vitamin D supplementation. HCN3 expression was significantly reduced in both Vitamin D-treated groups, while HCN4 was upregulated in testosterone-treated groups compared to the controls.
These findings suggest that HCN channels may play a role in the vascular alterations observed in PCOS and indicate a potential cardiovascular benefit of ivabradine in this condition.

Funded by the Department of Physhiology Semmelweis University