Jung Seung Hyo, Won Kyung-Jong, Lee Kang Pa, Kim Hyun-Joong, Seo Eun-Hye, Lee Hwan Myung, Park Eun Seok, Lee Seung Hyun, Kim Bokyung
*Department of Physiology, School of Medicine, Konkuk University, Chungju, Korea.
†Department of Cardiovascular Medicine, School of Medicine, Konkuk University, Chungju, Korea.
Clin Sci (Lond). 2015 Jul;129(1):27-38. doi: 10.1042/CS20140462.
The rupture of an atherosclerotic plaque is one of the main causes of coronary artery thrombotic occlusion, leading to myocardial infarction. However, the exact mechanism and causal risk factors for plaque rupture remain unclear. To identify a potential molecule that can influence atherosclerotic plaque rupture, we investigated protein expression in serum from patients with acute myocardial infarction (AMI) and stable angina (SA), using proteomic analysis. The expression of six proteins, including fibrinogen, fetuin-B, keratin 9, proapolipoprotein and fibrinogen, were altered in serum from patients with AMI compared with serum from those with SA. Of these, fetuin-B, proapolipoprotein, fibrinogen γ-B-chain precursors and fibrinogen expression were greater in serum from patients with AMI than from patients with SA. Increased fetuin-B expression in serum from AMI patients was also confirmed by Western blot analysis. Treatment with recombinant human fetuin-B increased the migration in monocytes and macrophages in a concentration-dependent manner. Fetuin-B also affected vascular plaque-stabilizing factors, including lipid deposition and cytokine production in macrophages, the activation of matrix metalloproteinase (MMP)-2 in monocytes, and the activation of apoptosis and MMP-2 in vascular smooth muscle cells. Moreover, in vivo administration of fetuin-B decreased the collagen accumulation and smooth muscle cell content and showed an increased number of macrophages in the vascular plaque. From these results, we suggest that fetuin-B may act as a modulator in the development of AMI. This study may provide a therapeutic advantage for patients at high risk of AMI.
动脉粥样硬化斑块破裂是冠状动脉血栓闭塞的主要原因之一,可导致心肌梗死。然而,斑块破裂的确切机制和因果风险因素仍不清楚。为了确定一种可能影响动脉粥样硬化斑块破裂的潜在分子,我们使用蛋白质组学分析方法,研究了急性心肌梗死(AMI)患者和稳定型心绞痛(SA)患者血清中的蛋白质表达情况。与SA患者的血清相比,AMI患者血清中六种蛋白质的表达发生了改变,包括纤维蛋白原、胎球蛋白-B、角蛋白9、载脂蛋白原和纤维蛋白原。其中,胎球蛋白-B、载脂蛋白原、纤维蛋白原γ-B链前体和纤维蛋白原在AMI患者血清中的表达高于SA患者。Western印迹分析也证实了AMI患者血清中胎球蛋白-B表达增加。重组人胎球蛋白-B处理以浓度依赖的方式增加了单核细胞和巨噬细胞的迁移。胎球蛋白-B还影响血管斑块稳定因子,包括巨噬细胞中的脂质沉积和细胞因子产生、单核细胞中基质金属蛋白酶(MMP)-2的激活以及血管平滑肌细胞中细胞凋亡和MMP-2的激活。此外,在体内给予胎球蛋白-B可减少血管斑块中的胶原蛋白积累和平滑肌细胞含量,并使巨噬细胞数量增加。基于这些结果,我们认为胎球蛋白-B可能在AMI的发生发展中起调节作用。本研究可能为AMI高危患者提供治疗优势。