The serum protein fetuin-B is involved in the development of acute myocardial infarction

• Published in: Clinical science (1979) Vol. 129; no. 1; pp. 27 - 38
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: England 01.07.2015
• Subjects: Aged; Angina, Stable - blood; Angina, Stable - metabolism; Animals; Apoptosis - drug effects; Blood Proteins - metabolism; Blotting, Western; Cell Line; Cell Movement - drug effects; Cytokines - metabolism; Electrophoresis, Gel, Two-Dimensional; Female; Fetuin-B - genetics; Fetuin-B - metabolism; Fetuin-B - pharmacology; Humans; Macrophages - drug effects; Macrophages - metabolism; Male; Matrix Metalloproteinase 2 - metabolism; Mice, Inbred C57BL; Middle Aged; Muscle, Smooth, Vascular - cytology; Myocardial Infarction - blood; Myocardial Infarction - metabolism; Myocytes, Smooth Muscle - drug effects; Myocytes, Smooth Muscle - metabolism; Proteome - metabolism; Proteomics - methods; Recombinant Proteins - pharmacology; U937 Cells
• ISSN: 0143-5221; 1470-8736
• 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.