2026-04-30T06:56:23Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/77202024-09-27T09:13:27Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605col_20.500.12105_19607
Repisalud
author
del Campo, Lara
author
Sanchez-Lopez, Amanda
author
Salaices, Mercedes
author
von Kleeck, Ryan A
author
Exposito, Elias
author
Gonzalez-Gomez, Cristina
author
Cusso, Lorena
author
Guzman-Martinez, Gabriela
author
Ruiz-Cabello, Jesus
author
Desco, Manuel
author
Assoian, Richard K
author
Briones, Ana M
author
Andres, Vicente
funder
Ministerio de Ciencia, Innovación y Universidades (España)
funder
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
funder
National Institutes of Health (Estados Unidos)
funder
Centro de Investigación Biomédica en Red - CIBERCV (Enfermedades Cardiovasculares)
funder
Instituto de Salud Carlos III
funder
Fundación ProCNIC
2019-06-04T10:48:53Z
2019-06-04T10:48:53Z
2019-06
Aging Cell. 2019; 18(3):e12936
10.1111/acel.12936
1474-9726
1474-9718
Aging cell
30884114
http://hdl.handle.net/20.500.12105/7720
Vascular stiffness is a major cause of cardiovascular disease during normal aging and in Hutchinson-Gilford progeria syndrome (HGPS), a rare genetic disorder caused by ubiquitous progerin expression. This mutant form of lamin A causes premature aging associated with cardiovascular alterations that lead to death at an average age of 14.6 years. We investigated the mechanisms underlying vessel stiffness in LmnaG609G/G609G mice with ubiquitous progerin expression, and tested the effect of treatment with nitrites. We also bred LmnaLCS/LCS Tie2Cre+/tg and LmnaLCS/LCS SM22αCre+/tg mice, which express progerin specifically in endothelial cells (ECs) and in vascular smooth muscle cells (VSMCs), respectively, to determine the specific contribution of each cell type to vascular pathology. We found vessel stiffness and inward remodeling in arteries of LmnaG609G/G609G and LmnaLCS/LCS SM22αCre+/tg , but not in those from LmnaLCS/LCS Tie2Cre+/tg mice. Structural alterations in aortas of progeroid mice were associated with decreased smooth muscle tissue content, increased collagen deposition, and decreased transverse waving of elastin layers in the media. Functional studies identified collagen (unlike elastin and the cytoskeleton) as an underlying cause of aortic stiffness in progeroid mice. Consistent with this, we found increased deposition of collagens III, IV, V, and XII in the media of progeroid aortas. Vessel stiffness and inward remodeling in progeroid mice were prevented by adding sodium nitrite in drinking water. In conclusion, LmnaG609G/G609G arteries exhibit stiffness and inward remodeling, mainly due to progerin-induced damage to VSMCs, which causes increased deposition of medial collagen and a secondary alteration in elastin structure. Treatment with nitrites prevents vascular stiffness in progeria.
eng
Aging
Dietary nitrite
Progeria
Smooth muscle cells
Vascular stiffness
Vascular smooth muscle cell-specific progerin expression in a mouse model of Hutchinson-Gilford progeria syndrome promotes arterial stiffness: Therapeutic effect of dietary nitrite
journal article
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