Curcumin protects against myocardial infarction-induced cardiac fibrosis via SIRT1 activation in vivo and in vitro.
Curcumin, a polyphenolic compound derived from turmeric, protects against myocardial injury by alleviating oxidative stress, inflammation, apoptosis, and fibrosis. However, the role of curcumin and its mechanism of action on interstitial fibrosis after myocardial infarction (MI) are poorly understood. To clarify, MI was induced by a permanent ligation of the left anterior descending coronary artery in adult mice, and the effects of curcumin were evaluated 4 weeks after the MI event. In vitro, we treated cardiac fibroblasts (CFs) with Ang II, and investigated the anti-fibrotic mechanism of curcumin. Our results showed that curcumin significantly attenuated collagen deposition in vivo and inhibited CF proliferation and migration, and MMP expression. In addition, we found that the down-regulation of SIRT1 after MI was attenuated by curcumin pretreatment, which indicated that the activation of SIRT1 might be involved in the protective action of curcumin. This hypothesis was confirmed by genetic inhibition of SIRT1 (siRNA-SIRT1) in Ang II-treated CFs. Our results provide new insights into the mechanism underlying the anti-fibrotic effects of curcumin in the heart.
Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan, Shandong, People's Republic of China.
Jie
J
Xiao
Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan, Shandong, People's Republic of China.
Xi
X
Sheng
Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan, Shandong, People's Republic of China.
Xinyu
X
Zhang
Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan, Shandong, People's Republic of China.
Mengqi
M
Guo
Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan, Shandong, People's Republic of China.
Xiaoping
X
Ji
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D003474:Curcumin / Q000494:pharmacology* / Q000627:therapeutic use; D004789:Enzyme Activation / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005355:Fibrosis / Q000188:drug therapy / Q000209:etiology* / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000150:complications* / Q000473:pathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism*; D013329:Structure-Activity Relationship
D000804:Angiotensin II; C470545:Sirt1 protein, mouse; C488368:Sirt1 protein, rat; D056564:Sirtuin 1; D003474:Curcumin
SIRT1; angiotensin II; cardiac fibroblasts; curcumin; fibrosis; myocardial infarction