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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\u2212\/\u2212 and Apoe\u2212\/\u2212 Nod1\u2212\/\u2212 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\u2212\/\u2212 atherosclerosis model suggests that NOD1 deficiency may decrease the risk of atherothrombosis by decreasing leukocyte infiltration and reducing macrophage apoptosis. Furthermore, Nod1\u2212\/\u2212 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.<\/jats:p>","DOI":"10.3390\/cells9092067","type":"journal-article","created":{"date-parts":[[2020,9,10]],"date-time":"2020-09-10T22:58:01Z","timestamp":1599778681000},"page":"2067","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Deletion or Inhibition of NOD1 Favors Plaque Stability and Attenuates Atherothrombosis in Advanced Atherogenesis"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0903-2247","authenticated-orcid":false,"given":"Silvia","family":"Gonz\u00e1lez-Ramos","sequence":"first","affiliation":[{"name":"Instituto de Investigaciones Biom\u00e9dicas Alberto Sols (CSIC-UAM), 28029 Madrid, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Enfermedades Cardiovasculares (CIBERCV), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria","family":"Fern\u00e1ndez-Garc\u00eda","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones Biom\u00e9dicas Alberto Sols (CSIC-UAM), 28029 Madrid, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Enfermedades Cardiovasculares (CIBERCV), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5485-1420","authenticated-orcid":false,"given":"Miriam","family":"Recalde","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones Biom\u00e9dicas Alberto Sols (CSIC-UAM), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6472-5647","authenticated-orcid":false,"given":"Cristina","family":"Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Enfermedades Cardiovasculares (CIBERCV), 28029 Madrid, Spain"},{"name":"Institut de Recerca del Hospital de la Santa Creu i Sant Pau-Programa ICCC, IIB Sant Pau, 08041 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3894-7166","authenticated-orcid":false,"given":"Jos\u00e9","family":"Mart\u00ednez-Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Enfermedades Cardiovasculares (CIBERCV), 28029 Madrid, Spain"},{"name":"Instituto de Investigaciones Biom\u00e9dicas de Barcelona (IIBB-CSIC), IIB Sant Pau, 08041 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0125-7209","authenticated-orcid":false,"given":"Vicente","family":"Andr\u00e9s","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Enfermedades Cardiovasculares (CIBERCV), 28029 Madrid, Spain"},{"name":"Laboratory of Molecular and Genetic Cardiovascular Pathophysiology, Vascular Pathophysiology Area, Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paloma","family":"Mart\u00edn-Sanz","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones Biom\u00e9dicas Alberto Sols (CSIC-UAM), 28029 Madrid, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas y Digestivas (CIBERehd), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0253-5469","authenticated-orcid":false,"given":"Lisardo","family":"Bosc\u00e1","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones Biom\u00e9dicas Alberto Sols (CSIC-UAM), 28029 Madrid, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Enfermedades Cardiovasculares (CIBERCV), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,9,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1093\/eurheartj\/ehs411","article-title":"Update on acute coronary syndromes: The pathologists\u2019 view","volume":"34","author":"Falk","year":"2013","journal-title":"Eur. 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