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We recently reviewed the capacity of cardiomyocytes to initiate inflammation, by means of expressing certain immune receptors such as toll\u2010like receptors (<jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content>s) that respond to pathogen\u2010 and damage\u2010associated molecular patterns (<jats:styled-content style=\"fixed-case\">PAMP<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">DAMP<\/jats:styled-content>). Previous studies observed <jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content>4\u2010mediated inflammation within days of myocardial infarction (<jats:styled-content style=\"fixed-case\">MI<\/jats:styled-content>). This study examined <jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content>4 expression and function in cardiomyocytes of failing hearts after 4\u00a0weeks of <jats:styled-content style=\"fixed-case\">MI<\/jats:styled-content> in rats. The increases of <jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content>4 <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> and proteins, as well as inflammatory cytokine production, were observed in both the infarct and remote myocardium. Enhanced immunostaining for <jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content>4 was observed in cardiomyocytes but not infiltrating leucocytes. The injection of lentivirus sh<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> against <jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content>4 into the infarcted heart decreased inflammatory cytokine production and improved heart function <jats:italic>in\u00a0vivo<\/jats:italic>. Accordingly, in cardiomyocytes isolated from <jats:styled-content style=\"fixed-case\">CHF<\/jats:styled-content> hearts, increases of <jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content>4 <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> and proteins were detected. More robust binding of <jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content>4 with lipopolysaccharide (<jats:styled-content style=\"fixed-case\">LPS<\/jats:styled-content>), a <jats:styled-content style=\"fixed-case\">PAMP<\/jats:styled-content> ligand for <jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content>4, and heat shock protein 60 (<jats:styled-content style=\"fixed-case\">HSP<\/jats:styled-content>60), a <jats:styled-content style=\"fixed-case\">DAMP<\/jats:styled-content> ligand for <jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content>4, was observed in <jats:styled-content style=\"fixed-case\">CHF<\/jats:styled-content> cardiomyocytes under a confocal microscope. The maximum binding capacity (B<jats:sub>max<\/jats:sub>) of <jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content>4 was increased for <jats:styled-content style=\"fixed-case\">LPS<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">HSP<\/jats:styled-content>60, whereas the binding affinity (Kd) was not significantly changed. Furthermore, both <jats:styled-content style=\"fixed-case\">LPS<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">HSP<\/jats:styled-content>60 induced more robust production of inflammatory cytokines in <jats:styled-content style=\"fixed-case\">CHF<\/jats:styled-content> cardiomyocytes, which was reduced by <jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content>4\u2010blocking antibodies. We conclude that the expression, ligand\u2010binding capacity and pro\u2010inflammatory function of cardiomyocyte <jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content>4 are up\u2010regulated after long\u2010term <jats:styled-content style=\"fixed-case\">MI<\/jats:styled-content>, which promote inflammation and exacerbate heart failure.<\/jats:p>","DOI":"10.1111\/jcmm.12659","type":"journal-article","created":{"date-parts":[[2015,8,20]],"date-time":"2015-08-20T09:45:07Z","timestamp":1440063907000},"page":"2728-2740","source":"Crossref","is-referenced-by-count":161,"title":["Up\u2010regulated <scp>TLR<\/scp>4 in cardiomyocytes exacerbates heart failure after long\u2010term myocardial infarction"],"prefix":"10.1111","volume":"19","author":[{"given":"Li","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Physiology and Key Lab of Ministry of Education in Fertility Preservation and Maintenance Ningxia Medical University Yinchuan 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