2026-04-18T13:44:46Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/162182024-09-27T09:16:47Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605
Repisalud
author
Macías, Álvaro
author
Nevado, Rosa M
author
González-Gómez, Cristina
author
Gonzalo, Pilar
author
Andres-Manzano, Maria J.
author
Dorado, Beatriz
author
Benedicto, Ignacio
author
Andres, Vicente
funder
Agencia Estatal de Investigación (España)
funder
Unión Europea. Fondo Social Europeo (ESF/FSE)
funder
Ministerio de Ciencia e Innovación (España)
funder
Ministerio de Educación, Cultura y Deporte (España)
funder
Comunidad de Madrid (España)
funder
Instituto de Salud Carlos III
funder
Fundación ProCNIC
funder
Ministerio de Ciencia e Innovación. Centro de Excelencia Severo Ochoa (España)
2023-07-07T08:27:59Z
2023-07-07T08:27:59Z
2023-05-26
Geroscience. 2023 May 26.
http://hdl.handle.net/20.500.12105/16218
10.1007/s11357-023-00808-3
2509-2723
Hutchinson-Gilford progeria syndrome (HGPS) is an extremely rare genetic disease caused by expression of progerin, a lamin A variant that is also expressed at low levels in non-HGPS individuals. Although HGPS patients die predominantly from myocardial infarction and stroke, the mechanisms that provoke pathological alterations in the coronary and cerebral arteries in HGPS remain ill defined. Here, we assessed vascular function in the coronary arteries (CorAs) and carotid arteries (CarAs) of progerin-expressing LmnaG609G/G609G mice (G609G), both in resting conditions and after hypoxic stimulus. Wire myography, pharmacological screening, and gene expression studies demonstrated vascular atony and stenosis, as well as other functional alterations in progeroid CorAs and CarAs and aorta. These defects were associated with loss of vascular smooth muscle cells and overexpression of the KV7 family of voltage-dependent potassium channels. Compared with wild-type controls, G609G mice showed reduced median survival upon chronic isoproterenol exposure, a baseline state of chronic cardiac hypoxia characterized by overexpression of hypoxia-inducible factor 1α and 3α genes, and increased cardiac vascularization. Our results shed light on the mechanisms underlying progerin-induced coronary and carotid artery disease and identify KV7 channels as a candidate target for the treatment of HGPS.
eng
Coronary and carotid artery dysfunction and KV7 overexpression in a mouse model of Hutchinson-Gilford progeria syndrome.
journal article
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URL
https://repisalud.isciii.es/bitstreams/bc801c99-c449-490f-a5e6-6451405aa834/download
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Coronary and carotid artery_Geroscience 2023.pdf
URL
https://repisalud.isciii.es/bitstreams/e241ccb1-bbe9-4c43-8197-d64795fc66d8/download
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Coronary and carotid artery_Geroscience 2023.pdf.txt