title: Curcumin reduces the cardiac ischemia-reperfusion injury: involvement of the toll-like receptor 2 in cardiomyocytes.
abstract: Curcumin, a polyphenolic compound derived from turmeric, has protective effects on myocardial injury through attenuation of oxidative stress and inflammation. Toll-like receptor 2 (TLR2), a key mediator of the innate immune system, is involved in myocardial infarction and examined if controlled by curcumin. Rat cardiomyocytes (CMs) were stimulated with tumor necrosis factor (TNF)-α, peptidoglycan (PGN) or hypoxia/reoxygenation (H/R) with or without curcumin pretreatment. Sprague-Dawley rats were fed curcumin (300 mg/kg/day) 1 week before cardiac ischemia/reperfusion (I/R) injury. The expression level of TLR2 and cardiac function were assessed. Both mRNA and protein of TLR2 were up-regulated in infarcted myocardium, while TLR4 remained unchanged. In CMs, TLR2 and monocyte chemoattractant protein (MCP)-1 mRNAs were increased by TNF-α, PGN or H/R, whereas they were blunted by curcumin. Immunofluorescence staining of CMs also showed that TLR2 and MCP-1 were increased after H/R, whereas curcumin-pretreated CMs were not. In animal study, 2 weeks after I/R, TLR2 was increased in the infarct zone, whereas it stayed unchanged in the Cur+I/R group. Macrophage infiltration (CD68), high-mobility group box 1 and fibrosis were increased in the I/R group, whereas they were decreased in the Cur+I/R group. Connexin 43 was reduced in the I/R group, while it recovered significantly in the Cur+I/R group. Cardiac contractility in the Cur+I/R group was also improved compared with that in the I/R group (max dp/dt in Cur+I/R group: 9660±612 vs. I/R group: 8119±366, P<.05). These results suggest that selective inhibition of TLR2 by curcumin could be preventive and therapeutic for myocardial infarction.
authors.affiliation: Heart Research Center, Chonnam National University Hospital, Gwangju, South Korea.
authors.forename: Yong Sook
authors.initials: YS
authors.lastname: Kim
authors.forename: Jin Sook
authors.initials: JS
authors.lastname: Kwon
authors.forename: Young Kuk
authors.initials: YK
authors.lastname: Cho
authors.forename: Myung Ho
authors.initials: MH
authors.lastname: Jeong
authors.forename: Jeong Gwan
authors.initials: JG
authors.lastname: Cho
authors.forename: Jong Chun
authors.initials: JC
authors.lastname: Park
authors.forename: Jung Chaee
authors.initials: JC
authors.lastname: Kang
authors.forename: Youngkeun
authors.initials: Y
authors.lastname: Ahn
mesh_terms: D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology*; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D003474:Curcumin / Q000494:pharmacology*; D024243:HMGB1 Protein / Q000235:genetics / Q000378:metabolism; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism; D010457:Peptidoglycan / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D015854:Up-Regulation
chemical_list: D002316:Cardiotonic Agents; C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D024243:HMGB1 Protein; C104200:Hbp1 protein, rat; D010457:Peptidoglycan; C495343:Tlr2 protein, rat; C495347:Tlr4 protein, rat; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D003474:Curcumin