TLR4 and atherosclerosis: However, although the role of TLR4 is well established in the early phase and in the progression of atherosclerosis, as shown by studies in knockout mice (Björkbacka et al., 2004; Michelsen et al., 2004; Higashimori et al., 2011), its role in advanced and unstable atherosclerotic plaques has yet to be fully assessed, and few studies point to an association between TLR4 activation and plaque rupture (Methe et al., 2005; Geng et al., 2006; Ishikawa et al., 2008).