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: Yong Sook Kim, Jin Sook Kwon, Young Kuk Cho, Myung Ho Jeong, Jeong Gwan Cho, Jong Chun Park, Jung Chaee Kang, Youngkeun Ahn
• Journal: The Journal of nutritional biochemistry (J Nutr Biochem) Vol. 23 Issue 11 Pg. 1514-23 (Nov 2012) ISSN: 1873-4847 [Electronic] United States
• PMID: 22402367 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Inc. All rights reserved.

Chemical References

• Cardiotonic Agents
• Ccl2 protein, rat
• Chemokine CCL2
• HMGB1 Protein
• Hbp1 protein, rat
• Peptidoglycan
• Tlr2 protein, rat
• Tlr4 protein, rat
• Toll-Like Receptor 2
• Toll-Like Receptor 4
• Tumor Necrosis Factor-alpha
• Curcumin

Topics

• Animals
• Cardiotonic Agents (pharmacology)
• Chemokine CCL2 (genetics, metabolism)
• Curcumin (pharmacology)
• HMGB1 Protein (genetics, metabolism)
• Male
• Myocardial Infarction (drug therapy, metabolism, pathology)
• Myocardial Reperfusion Injury (prevention & control)
• Myocytes, Cardiac (drug effects, metabolism)
• Peptidoglycan (pharmacology)
• Rats
• Rats, Sprague-Dawley
• Toll-Like Receptor 2 (genetics, metabolism)
• Toll-Like Receptor 4 (genetics, metabolism)
• Tumor Necrosis Factor-alpha (pharmacology)
• Up-Regulation