RT Journal Article
T1 Vitamin D Receptor Deficiency Upregulates Pulmonary Artery Kv7 Channel Activity
A1 Olivencia Plaza, Miguel Ángel
A1 Villegas Esguevillas, Marta
A1 Sancho González, María
A1 Barreira, Bianca
A1 Paternoster, Elena
A1 Adão, Rui
A1 Larriba, María Jesús
A1 Cogolludo Torralba, Ángel Luis
A1 Pérez Vizcaíno, Francisco
AB Recent evidence suggests that vitamin D is involved in the development of pulmonary arterial hypertension (PAH). The aim of this study was to analyze the electrophysiological and contractile properties of pulmonary arteries (PAs) in vitamin D receptor knockout mice (Vdr−/−). PAs were dissected and mounted in a wire myograph. Potassium membrane currents were recorded in freshly isolated PA smooth muscle cells (PASMCs) using the conventional whole-cell configuration of the patch-clamp technique. Potential vitamin D response elements (VDREs) in Kv7 channels coding genes were studied, and their protein expression was analyzed. Vdr−/− mice did not show a pulmonary hypertensive phenotype, as neither right ventricular hypertrophy nor endothelial dysfunction was apparent. However, resistance PA from these mice exhibited increased response to retigabine, a Kv7 activator, compared to controls and heterozygous mice. Furthermore, the current sensitive to XE991, a Kv7 inhibitor, was also higher in PASMCs from knockout mice. A possible VDRE was found in the gene coding for KCNE4, the regulatory subunit of Kv7.4. Accordingly, Vdr−/− mice showed an increased expression of KCNE4 in the lungs, with no changes in Kv7.1 and Kv7.4. These results indicate that the absence of Vdr in mice, as occurred with vitamin D deficient rats, is not sufficient to induce PAH. However, the contribution of Kv7 channel currents to the regulation of PA tone is increased in Vdr−/− mice, resembling animals and humans suffering from PAH.
PB MDPI
SN 1422-0067
YR 2023
FD 2023-08-02
LK https://hdl.handle.net/20.500.14352/105430
UL https://hdl.handle.net/20.500.14352/105430
LA eng
NO Olivencia, M.A.; Villegas-Esguevillas, M.; Sancho, M.; Barreira, B.; Paternoster, E.; Adão, R.; Larriba, M.J.; Cogolludo, A.; Perez-Vizcaino, F. Vitamin D Receptor Deficiency Upregulates Pulmonary Artery Kv7 Channel Activity. Int. J. Mol. Sci. 2023, 24, 12350. https://doi.org/10.3390/ijms241512350
NO Horizonte 2020.Marie-Curie Nº 847635.
NO European Commission
NO Instituto de Salud Carlos III (España)
NO Agencia Estatal de Investigación (España)
NO Universidad Complutense de Madrid
DS Docta Complutense
RD 6 abr 2025