Cao Jiatian, Ye Bozhi, Lin Lu, Tian Lei, Yang Hongbo, Wang Changqian, Huang Weijian, Huang Zhouqing
Division of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan UniversityShanghai, China; Division of Cardiology, School of Medicine, Shanghai Ninth Hospital, Shanghai Jiao Tong UniversityShanghai, China.
Division of Cardiology, The Key Lab of Cardiovascular Disease of Wenzhou, The First Affiliated Hospital of WenZhou Medical University WenZhou, China.
Front Pharmacol. 2017 Feb 14;8:62. doi: 10.3389/fphar.2017.00062. eCollection 2017.
Rupture of vulnerable atherosclerotic plaques is the leading cause of acute myocardial infarction (AMI) and unstable angina pectoris (UA). However, it still lacks an effective therapy to stabilize the vulnerable atherosclerotic plaques. Numerous reports have shown that upregulation of MMP-9 (matrix metalloproteinase-9) and EMMPRIN (extracellular matrix metalloproteinase inducer) in macrophages is involved in the progression and development of vulnerable plaques. Here we evaluated the impact of curcumin on the expression of MMP-9 and EMMPRIN in macrophages. Macrophages were pretreated with curcumin or specific inhibitors (p38 MAPK inhibitor, NF-κB p65 inhibitor) for 1 h, then cells were cultured with oxLDL for indicated time. Real-time PCR and Western blot analysis were used to evaluate the expression of mRNA and proteins. Translocation of NF-κB p65 was detected by using laser confocal microscopy. Here we showed that curcumin attenuated the MMP-9 and EMMPRIN expression in oxLDL stimulated macrophages. Further studies revealed that curcumin inhibited oxLDL induced NF-κB activation and p38 MAPK phosphorylation. These findings illustrated that curcumin can inhibit the expression of EMMPRIN and MMP-9 in oxLDL stimulated macrophages through down regulation of NF-κB and p38 MAPK signaling pathways, which might be the molecular mechanism for the anti-atherosclerotic effect of curcumin.
易损动脉粥样硬化斑块破裂是急性心肌梗死（AMI）和不稳定型心绞痛（UA）的主要原因。然而，目前仍缺乏稳定易损动脉粥样硬化斑块的有效治疗方法。大量报道表明，巨噬细胞中基质金属蛋白酶-9（MMP-9）和细胞外基质金属蛋白酶诱导剂（EMMPRIN）的上调参与了易损斑块的进展和发展。在此，我们评估了姜黄素对巨噬细胞中MMP-9和EMMPRIN表达的影响。巨噬细胞先用姜黄素或特异性抑制剂（p38丝裂原活化蛋白激酶抑制剂、NF-κB p65抑制剂）预处理1小时，然后用氧化型低密度脂蛋白（oxLDL）培养指定时间。采用实时聚合酶链反应（PCR）和蛋白质印迹分析来评估mRNA和蛋白质的表达。使用激光共聚焦显微镜检测NF-κB p65的转位。在此我们发现，姜黄素可减弱oxLDL刺激的巨噬细胞中MMP-9和EMMPRIN的表达。进一步研究表明，姜黄素可抑制oxLDL诱导的NF-κB活化和p38丝裂原活化蛋白激酶磷酸化。这些发现表明，姜黄素可通过下调NF-κB和p38丝裂原活化蛋白激酶信号通路来抑制oxLDL刺激的巨噬细胞中EMMPRIN和MMP-9的表达，这可能是姜黄素抗动脉粥样硬化作用的分子机制。
