RT info:eu-repo/semantics/article
T1 Kv1.3 Channel Inhibition Limits Uremia-Induced Calcification in Mouse and Human Vascular Smooth Muscle
A1 Cazaña Pérez, Violeta
A1 Cidad Velasco, María del Pilar
A1 Navarro-González, Juan F.
A1 Rojo Mencía, Jorge
A1 Jaisser, Frederic
A1 López López, José Ramón
A1 Álvarez de la Rosa, Diego
A1 Giraldez, Teresa
A1 Pérez García, María Teresa
AB Chronic kidney disease (CKD) significantly increases cardiovascular risk. In advanced CKD stages, accumulation of toxic circulating metabolites and mineral metabolism alterations triggers vascular calcification, characterized by vascular smooth muscle cell (VSMC) transdifferentiation and loss of the contractile phenotype. Phenotypic modulation of VSMC occurs with significant changes in gene expression. Even though ion channels are an integral component of VSMC function, the effects of uremia on ion channel remodeling has not been explored. We used an in vitro model of uremia-induced calcification of human aorta smooth muscle cells (HASMCs) to study the expression of 92 ion channel subunit genes. Uremic serum-induced extensive remodeling of ion channel expression consistent with loss of excitability but different from the one previously associated with transition from contractile to proliferative phenotypes. Among the ion channels tested, we found increased abundance and activity of voltage-dependent K+ channel Kv1.3. Enhanced Kv1.3 expression was also detected in aorta from a mouse model of CKD. Pharmacological inhibition or genetic ablation of Kv1.3 decreased the amount of calcium phosphate deposition induced by uremia, supporting an important role for this channel on uremia-induced VSMC calcification.
YR 2021
FD 2021
LK https://uvadoc.uva.es/handle/10324/65378
UL https://uvadoc.uva.es/handle/10324/65378
LA spa
NO Function, Volume 2, Issue 1, 2021, zqaa036, https://doi.org/10.1093/function/zqaa036
DS UVaDOC
RD 17-jul-2024