2026-06-29T16:41:49Zhttps://docta.ucm.es/rest/oai/requestoai:docta.ucm.es:20.500.14352/1367562026-05-19T23:53:24Zcom_20.500.14352_14col_20.500.14352_15
Docta Complutense
author
Kowalewska, Paulina M
author
Sancho González, María
author
Fabris, Sergio
author
Huff, Murray W
author
Gros, Robert
author
Welsh, Donald G
2026-05-19T09:02:27Z
2026-05-19T09:02:27Z
2025-12-07
Kowalewska PM, Sancho M, Fabris S, Huff MW, Gros R, Welsh DG. From cells to organism: impact of dyslipidemia on inwardly rectifying K+ channels and cerebral vascular function. J Cereb Blood Flow Metab. 2025 Dec 7:271678X251399019. doi: 10.1177/0271678X251399019.
10.1177/0271678X251399019
https://hdl.handle.net/20.500.14352/136756
https://doi.org/10.1177/0271678X251399019
41355035
https://journals.sagepub.com/doi/10.1177/0271678X251399019
Evidence increasingly suggests that dyslipidemia diminishes dilatory function of resistance arteries by altering ion channel activity. Focusing on the cerebral vasculature, this study investigated whether inwardly rectifying K 2.1 (K2.1) channels are targeted early in dyslipidemia. Experiments began at the cellular level (patch-clamp electrophysiology), then progressed to isolated arteries (pressure myography) and whole animals (arterial spin-labeling magnetic resonance imaging). Lipid analysis confirmed dyslipidemia in (normal chow) and C57BL/6 mice fed a high-fat high-cholesterol (HFHC) diet for 8 weeks; no aortic plaques were observed. Patch-clamp electrophysiology revealed a marked reduction in endothelial but not smooth muscle K activity in both dyslipidemic models; this K activity was recoverable by plasma membrane cholesterol depletion. These cellular changes notably diminished flow-induced vasodilation in cerebral arteries isolated from both dyslipidemic models; such deficits were observed in endothelial arteries. A blood pressure challenge induced a perfusion phenotype in HFHC-C57BL/6 but not genetic deletion () mice, consistent with reduced K activity and flow-mediated dilation. Our findings highlight that endothelial K2.1 channels are targeted early in dyslipidemia, which was associated with attenuated flow-mediated dilation in our acute HFHC model. This change likely moderates the range of blood flow control and substrate delivery to active brain tissue.
eng
Attribution-NonCommercial 4.0 International
From cells to organism: impact of dyslipidemia on inwardly rectifying K channels and cerebral vascular function.
journal article
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https://docta.ucm.es/bitstreams/ad7bbd6a-164f-47c2-b00d-c14fdbfac01c/download
File
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37f32771c922e84f0ca16268119a04ea
3076540
application/pdf
Kowalewska et al. (2025) Dyslipidemia impact on inwardly rectifying K⁺ channels and cerebral vascular function. J Cereb Blood Flow Metab.pdf