RT Journal Article
T1 Vitamin D deficiency downregulates TASK-1 channels and induces pulmonary vascular dysfunction
A1 Callejo Arranz, María
A1 Mondejar Parreño, Gema
A1 Morales Cano, Daniel
A1 Barreira, Bianca
A1 Esquivel Ruiz, Sergio Antonio
A1 Olivencia Plaza, Miguel Ángel
A1 Moreno Gutiérrez, Laura
A1 Cogolludo Torralba, Ángel Luis
A1 Pérez Vizcaíno, Francisco
AB Vitamin D (VitD) receptor regulates the expression of several genes involved in signaling pathways affected in pulmonary hypertension (PH). VitD deficiency is highly prevalent in PH, and low levels are associated with poor prognosis. We investigated if VitD deficiency may predispose to or exacerbate PH. Male Wistar rats were fed with a standard or a VitD-free diet for 5 wk. Next, rats were further divided into controls or PH, which was induced by a single dose of Su-5416 (20 mg/kg) and exposure to hypoxia (10% O2) for 2 wk. VitD deficiency had no effect on pulmonary pressure in normoxic rats, indicating that, by itself, it does not trigger PH. However, it induced several moderate but significant changes characteristic of PH in the pulmonary arteries, such as increased muscularization, endothelial dysfunction, increased survivin, and reduced bone morphogenetic protein (Bmp) 4, Bmp6, DNA damage-inducible transcript 4, and K+ two-pore domain channel subfamily K member 3 (Kcnk3) expression. Myocytes isolated from pulmonary arteries from VitD-deficient rats had a reduced whole voltage-dependent potassium current density and acid-sensitive (TASK-like) potassium currents. In rats with PH induced by Su-5416 plus hypoxia, VitD-free diet induced a modest increase in pulmonary pressure, worsened endothelial function, increased the hyperreactivity to serotonin, arterial muscularization, decreased total and TASK-1 potassium currents, and further depolarized the pulmonary artery smooth muscle cell membrane. In human pulmonary artery smooth muscle cells from controls and patients with PH, the active form of VitD calcitriol significantly increased KCNK3 mRNA expression. Altogether, these data strongly suggest that the deficit in VitD induces pulmonary vascular dysfunction.
PB American Physiological Society
SN 1040-0605
YR 2020
FD 2020-10-01
LK https://hdl.handle.net/20.500.14352/130071
UL https://hdl.handle.net/20.500.14352/130071
LA eng
NO Callejo M, Mondejar-Parreño G, Morales-Cano D, Barreira B, Esquivel-Ruiz S, Olivencia MA, Manaud G, Perros F, Duarte J, Moreno L, Cogolludo A, Perez-Vizcaíno F. Vitamin D deficiency downregulates TASK-1 channels and induces pulmonary vascular dysfunction. Am J Physiol Lung Cell Mol Physiol. 2020 Oct 1;319(4):L627-L640. doi: 10.1152/ajplung.00475.2019
DS Docta Complutense
RD 14 ene 2026