2026-04-29T07:22:15Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/111942024-09-27T09:45:08Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605
Repisalud
author
Nevado, Rosa M
author
Hamczyk, Magda R.
author
Gonzalo, Pilar
author
Andres-Manzano, Maria J.
author
Andres, Vicente
funder
Ministerio de Ciencia e Innovación (España)
funder
Instituto de Salud Carlos III
funder
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
funder
Progeria Research Foundation
funder
Ministerio de Educación, Cultura y Deporte (España)
funder
Fundación ProCNIC
2020-10-26T08:55:13Z
2020-10-26T08:55:13Z
2020-10-08
Cells. 2020; 9(10):E2252
http://hdl.handle.net/20.500.12105/11194
33049978
10.3390/cells9102252
2073-4409
Cells
Hutchinson-Gilford progeria syndrome (HGPS) is among the most devastating of the laminopathies, rare genetic diseases caused by mutations in genes encoding nuclear lamina proteins. HGPS patients age prematurely and die in adolescence, typically of atherosclerosis-associated complications. The mechanisms of HGPS-related atherosclerosis are not fully understood due to the scarcity of patient-derived samples and the availability of only one atheroprone mouse model of the disease. Here, we generated a new atherosusceptible model of HGPS by crossing progeroid LmnaG609G/G609G mice, which carry a disease-causing mutation in the Lmna gene, with Ldlr-/- mice, a commonly used preclinical atherosclerosis model. Ldlr-/-LmnaG609G/G609G mice aged prematurely and had reduced body weight and survival. Compared with control mice, Ldlr-/-LmnaG609G/G609G mouse aortas showed a higher atherosclerosis burden and structural abnormalities typical of HGPS patients, including vascular smooth muscle cell depletion in the media, adventitial thickening, and elastin structure alterations. Atheromas of Ldlr-/-LmnaG609G/G609G mice had features of unstable plaques, including the presence of erythrocytes and iron deposits and reduced smooth muscle cell and collagen content. Ldlr-/-LmnaG609G/G609G mice faithfully recapitulate vascular features found in patients and thus provide a new tool for studying the mechanisms of HGPS-related atherosclerosis and for testing therapies.
eng
Premature Vascular Aging with Features of Plaque Vulnerability in an Atheroprone Mouse Model of Hutchinson-Gilford Progeria Syndrome with Ldlr Deficiency.
journal article
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URL
https://repisalud.isciii.es/bitstreams/a048a4a3-0e49-423f-b8da-9d170b82cf49/download
File
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application/pdf
PrematureVascularAgingFeatures_2020.pdf
URL
https://repisalud.isciii.es/bitstreams/c192f8c3-e070-4249-8f58-28a8fca8a7ee/download
File
MD5
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text/plain
PrematureVascularAgingFeatures_2020.pdf.txt