Deletion or inhibition of NOD1 favors plaque stability and attenuates atherothrombosis in advanced atherogenesis
Editor
MDPI, Basel, SwitzerlandFecha de edición
2020-09-10Cita
10.3390/cells9092067
Cells 9.9 (2020): 2063
ISSN
2073-4409DOI
10.3390/cells9092067Financiado por
This work was supported by the Ministerio Economía, Industria y Competitividad/Agencia Estatal de Investigación (SAF2016-79490-R, RTI2018-094727-B-100, SAF2015-64767-R, SAF2016-75004-R, SAF2017-82436-R/RTC2017-6283-1, PID2019-108977RB-100), Centro de Investigación Biomédica en Red en Enfermedades Cardiovasculares (CB16/11/00405, CB16/11/00257, CB16/11/00222), Fundación Ramón Areces (CIUP18A3864), Consorcio de Investigación en Red de la Comunidad de Madrid, S2017/BMD-3686 and Fondo Europeo de Desarrollo Regional.Proyecto
Gobierno de España. SAF2016-79490-R; Gobierno de España. RTI2018-094727-B-100; Gobierno de España. SAF2015-64767-R; Gobierno de España. SAF2016-75004-R; Gobierno de España. SAF2017-82436-R/RTC2017-6283-1; Gobierno de España. PID2019-108977RB-100; Gobierno de España. CB16/11/00405; Gobierno de España. CB16/11/00257; Gobierno de España. CB16/11/00222; Comunidad de Madrid. S2017/BMD-3686/CIFRA2Versión del editor
http://doi.org/10.3390/cells9092067Materias
atherothrombosis; coronary disease; innate immunity; pattern recognition receptors; vulnerable plaque; MedicinaDerechos
© 2020 The AuthorsResumen
Atherothrombosis, the main cause of acute coronary syndromes (ACS), is characterized by the rupture of the atherosclerotic plaque followed by the formation of thrombi. Fatal plaque rupture sites show large necrotic cores combined with high levels of inflammation and thin layers of collagen. Plaque necrosis due to the death of macrophages and smooth muscle cells (SMCs) remains critical in the process. To determine the contribution of the innate immunity receptor NOD1 to the stability of atherosclerotic plaque, Apoe-/- and Apoe-/- Nod1-/- atherosclerosis prone mice were placed on a high-fat diet for 16 weeks to assess post-mortem advanced atherosclerosis in the aortic sinus. The proliferation and apoptosis activity were analyzed, as well as the foam cell formation capacity in these lesions and in primary cultures of macrophages and vascular SMCs obtained from both groups of mice. Our results reinforce the preeminent role for NOD1 in human atherosclerosis. Advanced plaque analysis in the Apoe-/- atherosclerosis model suggests that NOD1 deficiency may decrease the risk of atherothrombosis by decreasing leukocyte infiltration and reducing macrophage apoptosis. Furthermore, Nod1-/- SMCs exhibit higher proliferation rates and decreased apoptotic activity, contributing to thicker fibrous caps with reduced content of pro-thrombotic collagen. These findings demonstrate a direct link between NOD1 and plaque vulnerability through effects on both macrophages and SMCs, suggesting promising insights for early detection of biomarkers for treating patients before ACS occurs.
Lista de ficheros
Google Scholar:González-Ramos, Silvia
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Fernández-García, Victoria
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Recalde, Miriam
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Rodríguez, Cristina
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Martínez-González, José
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Andrés, Vicente
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Martín-Sanz, Paloma
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Boscá, Lisardo
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