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Therefore, blockade of inflammatory signal is a potential therapeutic management for MI\/R complicated with hyperlipidemia. Hydroxysafflor yellow A (HSYA, a monomer extracted from <jats:italic>Carthamus tinctorius<\/jats:italic> L.), was studied in this article to address that the regulation of inflammatory signal would alleviate MI\/R combined with hyperlipidemia injury. High-fat diet induced hyperlipidemia worsened MI\/R mediated heart injury (elevation of infarct size, CK-MB and LDH activity), activated TLR4 over-expression in hearts, released inflammatory cytokines (LPS, TNF-\u03b1 and IL-1\u03b2) excessively. HSYA administration suppressed the over-expression of TLR4 and alleviated heart damage caused by MI\/R complicated with hyperlipidemia. Furthermore, HSYA had little influence on MI\/R injury in TLR4-knockout mice, which indicated that HSYA protected MI\/R through TLR4 inhibition. <jats:italic>In vitro<\/jats:italic>, hypoxia\/reoxygenation (H\/R) coexisting with LPS model in neonatal rat ventricular myocytes (NRVMs) induced serious damage compared with H\/R injury to NRVMs. HSYA decreased excessive secretion of inflammatory cytokines, down-regulated over-expression of TLR4 and NF-\u03baB in H\/R\u2009+\u2009LPS injured NRVMs. In conclusion, HSYA alleviated myocardial inflammatory injury through suppressing TLR4, offering an alternative medication for MI\/R associated with hyperlipidemia.<\/jats:p>","DOI":"10.1038\/srep35319","type":"journal-article","created":{"date-parts":[[2016,10,12]],"date-time":"2016-10-12T09:33:46Z","timestamp":1476264826000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":53,"title":["Hydroxysafflor yellow A alleviates myocardial ischemia\/reperfusion in hyperlipidemic animals through the suppression of TLR4 signaling"],"prefix":"10.1038","volume":"6","author":[{"given":"Dan","family":"Han","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenhuan","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yidong","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nian","family":"Xia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongcheng","family":"Cai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunman","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weirong","family":"Fang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,10,12]]},"reference":[{"key":"BFsrep35319_CR1","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1172\/JCI62874","volume":"123","author":"DJ Hausenloy","year":"2013","unstructured":"Hausenloy, D. 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