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Association of SDF1 and MMP12 with Atherosclerosis and Inflammation: Clinical and Experimental Study

BACKGROUND: Atherosclerosis is the main etiology of cardiovascular diseases (CVD), associated to systemic inflammation. Matrix metalloproteinases (MMPs) are related to atherosclerosis progression through the SDF1/CXCR4 axis promoting macrophages recruitment within the vascular wall. The goal was to...

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Autores principales: Marcos-Jubilar, María, Orbe, Josune, Roncal, Carmen, Machado, Florencio J. D., Rodriguez, José Antonio, Fernández-Montero, Alejandro, Colina, Inmaculada, Rodil, Raquel, Pastrana, Juan C., Páramo, José A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8147178/
https://www.ncbi.nlm.nih.gov/pubmed/34062730
http://dx.doi.org/10.3390/life11050414
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author Marcos-Jubilar, María
Orbe, Josune
Roncal, Carmen
Machado, Florencio J. D.
Rodriguez, José Antonio
Fernández-Montero, Alejandro
Colina, Inmaculada
Rodil, Raquel
Pastrana, Juan C.
Páramo, José A.
author_facet Marcos-Jubilar, María
Orbe, Josune
Roncal, Carmen
Machado, Florencio J. D.
Rodriguez, José Antonio
Fernández-Montero, Alejandro
Colina, Inmaculada
Rodil, Raquel
Pastrana, Juan C.
Páramo, José A.
author_sort Marcos-Jubilar, María
collection PubMed
description BACKGROUND: Atherosclerosis is the main etiology of cardiovascular diseases (CVD), associated to systemic inflammation. Matrix metalloproteinases (MMPs) are related to atherosclerosis progression through the SDF1/CXCR4 axis promoting macrophages recruitment within the vascular wall. The goal was to assess new circulatory inflammatory markers in relation to atherosclerosis. METHODS: Measurement of SDF1, MMP12 and CRP in blood samples of 298 prospective patients with cardiovascular risk. To explore atherosclerosis progression, CXCR4/SDF1 axis and MMP12 expression were determined by RT-qPCR and by immunohistochemistry in the aorta of accelerated and delayed atherosclerosis mice models (Apoe-/- and Apoe-/-Mmp10-/-). RESULTS: SDF1, MMP12 and CRP were elevated in patients with clinical atherosclerosis, but after controlling by confounding factors, only SDF1 and CRP remained increased. Having high levels of both biomarkers showed 2.8-fold increased risk of presenting clinical atherosclerosis (p = 0.022). Patients with elevated SDF1, MMP12 and CRP showed increased risk of death in follow-up (HR = 3.2, 95%CI: 1.5–7.0, p = 0.004). Gene and protein expression of CXCR4 and MMP12 were increased in aortas from Apoe-/- mice. CONCLUSIONS: The combination of high circulating SDF1, MMP12 and CRP identified patients with particular inflammatory cardiovascular risk and increased mortality. SDF1/CXCR4 axis and MMP12 involvement in atherosclerosis development suggests that they could be possible atherosclerotic targets.
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spelling pubmed-81471782021-05-26 Association of SDF1 and MMP12 with Atherosclerosis and Inflammation: Clinical and Experimental Study Marcos-Jubilar, María Orbe, Josune Roncal, Carmen Machado, Florencio J. D. Rodriguez, José Antonio Fernández-Montero, Alejandro Colina, Inmaculada Rodil, Raquel Pastrana, Juan C. Páramo, José A. Life (Basel) Article BACKGROUND: Atherosclerosis is the main etiology of cardiovascular diseases (CVD), associated to systemic inflammation. Matrix metalloproteinases (MMPs) are related to atherosclerosis progression through the SDF1/CXCR4 axis promoting macrophages recruitment within the vascular wall. The goal was to assess new circulatory inflammatory markers in relation to atherosclerosis. METHODS: Measurement of SDF1, MMP12 and CRP in blood samples of 298 prospective patients with cardiovascular risk. To explore atherosclerosis progression, CXCR4/SDF1 axis and MMP12 expression were determined by RT-qPCR and by immunohistochemistry in the aorta of accelerated and delayed atherosclerosis mice models (Apoe-/- and Apoe-/-Mmp10-/-). RESULTS: SDF1, MMP12 and CRP were elevated in patients with clinical atherosclerosis, but after controlling by confounding factors, only SDF1 and CRP remained increased. Having high levels of both biomarkers showed 2.8-fold increased risk of presenting clinical atherosclerosis (p = 0.022). Patients with elevated SDF1, MMP12 and CRP showed increased risk of death in follow-up (HR = 3.2, 95%CI: 1.5–7.0, p = 0.004). Gene and protein expression of CXCR4 and MMP12 were increased in aortas from Apoe-/- mice. CONCLUSIONS: The combination of high circulating SDF1, MMP12 and CRP identified patients with particular inflammatory cardiovascular risk and increased mortality. SDF1/CXCR4 axis and MMP12 involvement in atherosclerosis development suggests that they could be possible atherosclerotic targets. MDPI 2021-05-01 /pmc/articles/PMC8147178/ /pubmed/34062730 http://dx.doi.org/10.3390/life11050414 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Marcos-Jubilar, María
Orbe, Josune
Roncal, Carmen
Machado, Florencio J. D.
Rodriguez, José Antonio
Fernández-Montero, Alejandro
Colina, Inmaculada
Rodil, Raquel
Pastrana, Juan C.
Páramo, José A.
Association of SDF1 and MMP12 with Atherosclerosis and Inflammation: Clinical and Experimental Study
title Association of SDF1 and MMP12 with Atherosclerosis and Inflammation: Clinical and Experimental Study
title_full Association of SDF1 and MMP12 with Atherosclerosis and Inflammation: Clinical and Experimental Study
title_fullStr Association of SDF1 and MMP12 with Atherosclerosis and Inflammation: Clinical and Experimental Study
title_full_unstemmed Association of SDF1 and MMP12 with Atherosclerosis and Inflammation: Clinical and Experimental Study
title_short Association of SDF1 and MMP12 with Atherosclerosis and Inflammation: Clinical and Experimental Study
title_sort association of sdf1 and mmp12 with atherosclerosis and inflammation: clinical and experimental study
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8147178/
https://www.ncbi.nlm.nih.gov/pubmed/34062730
http://dx.doi.org/10.3390/life11050414
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