2026-04-29T19:34:55Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/156402024-09-27T08:09:40Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605
Repisalud
author
Sahún-Español, Álvaro
author
Clemente, Cristina
author
Jiménez-Loygorri, Juan Ignacio
author
Sierra-Filardi, Elena
author
Herrera-Melle, Leticia
author
Gómez-Durán, Aurora
author
Sabio, Guadalupe
author
Monsalve, María
author
Boya, Patricia
author
Arroyo, Alicia G
funder
Ministerio de Ciencia e Innovación (España)
funder
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
funder
Unión Europea
funder
Ministerio de Educación, Cultura y Deporte (España)
funder
Fundación La Caixa
funder
Comunidad de Madrid (España)
2023-03-16T10:06:56Z
2023-03-16T10:06:56Z
2022-04-08
Sci Rep. 2022 Apr 8;12(1):5938
10.1038/s41598-022-09757-x
2045-2322
Scientific reports
35396524
http://hdl.handle.net/20.500.12105/15640
Vascular smooth muscle cell (VSMC) proliferation is essential for arteriogenesis to restore blood flow after artery occlusion, but the mechanisms underlying this response remain unclear. Based on our previous findings showing increased VSMC proliferation in the neonatal aorta of mice lacking the protease MT4-MMP, we aimed at discovering new players in this process. We demonstrate that MT4-MMP absence boosted VSMC proliferation in vitro in response to PDGF-BB in a cell-autonomous manner through enhanced p38 MAPK activity. Increased phospho-p38 in basal MT4-MMP-null VSMCs augmented the rate of mitochondrial degradation by promoting mitochondrial morphological changes through the co-activator PGC1α as demonstrated in PGC1α-/- VSMCs. We tested the in vivo implications of this pathway in a novel conditional mouse line for selective MT4-MMP deletion in VSMCs and in mice pre-treated with the p38 MAPK activator anisomycin. Priming of p38 MAPK activity in vivo by the absence of the protease MT4-MMP or by anisomycin treatment led to enhanced arteriogenesis and improved flow recovery after femoral artery occlusion. These findings may open new therapeutic opportunities for peripheral vascular diseases.
eng
p38 MAPK priming boosts VSMC proliferation and arteriogenesis by promoting PGC1α-dependent mitochondrial dynamics.
journal article
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p38 MAPK priming boosts Sci Rep 2022.pdf
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p38 MAPK priming boosts Sci Rep 2022.pdf.txt