{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T15:30:23Z","timestamp":1790695823819,"version":"4.1.0"},"reference-count":21,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"8","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2017,8]]},"abstract":"<jats:sec>\n                    <jats:title>Objective\u2014<\/jats:title>\n                    <jats:p>\n                      Inflammasomes are multiprotein complexes, and their activation has been associated with cardiovascular disease. Inflammasome activation leads to secretion of caspase-1 by innate immune cells, resulting in the activation of interleukin-1\u03b2. Recently, a potent and selective inhibitor of the NLRP3 inflammasome, MCC950, was described. In this study, we investigated the effect of MCC950 on atherosclerotic lesion development in apoE\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Approach and Results\u2014<\/jats:title>\n                    <jats:p>\n                      First, we determined the efficacy of MCC950 in vitro. Bone marrow\u2013derived macrophages and dendritic cells were stimulated with lipopolysaccharide and cholesterol crystals resulting in high levels of interleukin-1\u03b2 release, which was inhibited by MCC950. In vivo MCC950 treatment reduced lipopolysaccharide\u2013induced interleukin-1\u03b2 secretion, without affecting the tumor necrosis factor-\u03b1 response. Subsequently, atherosclerotic plaques were induced in Western-type diet fed apoE\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      mice by semiconstrictive perivascular collar placement at the carotid arteries, after which the mice received MCC950 (10 mg\/kg) or vehicle control 3\u00d7 per week intraperitoneally for 4 weeks. After euthanize, atherosclerotic plaque size and volume were quantified in hematoxylin-eosin\u2013stained 10-\u00b5m cryosections throughout the artery. MCC950 treatment significantly reduced the development of atherosclerotic lesions as determined by maximal stenosis, average plaque size, and plaque volume. Although the amount of collagen and the necrotic core size were not affected, the number of macrophages in the plaque was significantly reduced on treatment. In addition, VCAM-1 (vascular cell adhesion molecule 1) and ICAM-1 (intercellular adhesion molecule 1) mRNA expression was significantly reduced in the carotids of MCC950-treated mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions\u2014<\/jats:title>\n                    <jats:p>These findings show that specific inhibition of the NLRP3 inflammasome using MCC950 can be a promising therapeutic approach to inhibit atherosclerotic lesion development.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/atvbaha.117.309575","type":"journal-article","created":{"date-parts":[[2017,6,8]],"date-time":"2017-06-08T21:10:28Z","timestamp":1496956228000},"page":"1457-1461","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":330,"title":["NLRP3 Inflammasome Inhibition by MCC950 Reduces Atherosclerotic Lesion Development in Apolipoprotein E\u2013Deficient Mice\u2014Brief Report"],"prefix":"10.1161","volume":"37","author":[{"given":"Thomas","family":"van der Heijden","sequence":"first","affiliation":[{"name":"From the Cluster BioTherapeutics, LACDR, Leiden University, The Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Kritikou","sequence":"additional","affiliation":[{"name":"From the Cluster BioTherapeutics, LACDR, Leiden University, The Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wouter","family":"Venema","sequence":"additional","affiliation":[{"name":"From the Cluster BioTherapeutics, LACDR, Leiden University, The Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janine","family":"van Duijn","sequence":"additional","affiliation":[{"name":"From the Cluster BioTherapeutics, LACDR, Leiden University, The Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter J.","family":"van Santbrink","sequence":"additional","affiliation":[{"name":"From the Cluster BioTherapeutics, LACDR, Leiden University, The Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bram","family":"Sl\u00fctter","sequence":"additional","affiliation":[{"name":"From the Cluster BioTherapeutics, LACDR, Leiden University, The Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda C.","family":"Foks","sequence":"additional","affiliation":[{"name":"From the Cluster BioTherapeutics, LACDR, Leiden University, The Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilze","family":"Bot","sequence":"additional","affiliation":[{"name":"From the Cluster BioTherapeutics, LACDR, Leiden University, The Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johan","family":"Kuiper","sequence":"additional","affiliation":[{"name":"From the Cluster BioTherapeutics, LACDR, Leiden University, The 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