Cystatin C-Adiponectin Complex in Plasma Associates with Coronary Plaque Instability.
OBJECTIVE
Adiponectin (APN) is an adipocyte-derived bioactive molecule with antiatherogenic properties. We previously reported that cystatin C (CysC) abolished the anti-atherogenic effects of APN. We aimed to elucidate the clinical significance of CysC-APN complex in patients with coronary artery disease (CAD).


METHODS
We enrolled 43 stable CAD male patients to examine the relationship between CysC-APN complex and coronary plaque characteristics. Serum was immunoprecipitated by the anti-APN antibody and immunoblotted by the anti-CysC antibody to demonstrate the presence of CysC-APN complexes in vivo. To confirm their binding in vitro, HEK293T cell lysates overexpressing myc-APN and FLAG-CysC were immunoprecipitated with an anti-myc or anti-FLAG antibody, followed by immunoblotting with an anti-APN or anti-CysC antibody.


RESULTS
CysC was identified as a specific co-immunoprecipitant with APN by the anti-APN antibody in human serum. In vitro, FLAG-CysC was co-immunoprecipitated with myc-APN by the anti-myc antibody and myc-APN was co-immunoprecipitated with FLAG-CysC by the anti-FLAG antibody. Among CAD patients, serum CysC-APN complex levels negatively correlated with fibrotic components of coronary plaques and positively correlated with either necrotic or lipidic plus necrotic components. Plaque burden negatively correlated with serum APN levels but not serum CysC-APN complex levels. Serum CysC levels had no association with plaque characteristics. In multivariate analysis, CysC-APN complex levels were identified as the strongest negative factor for fibrotic components and the strongest positive factor for both necrotic and lipidic plus necrotic components.


CONCLUSIONS
Measuring serum CysC-APN complex levels is helpful for evaluating coronary plaque instability in CAD patients.
Department of Biomedical Informatics, Division of Health Sciences, Osaka University Graduate School of Medicine.
Akane
A
Matsumoto
Department of Biomedical Informatics, Division of Health Sciences, Osaka University Graduate School of Medicine.
Hiroyasu
H
Yamamoto
Department of Cardiology, Hyogo Prefectural Nishinomiya Hospital.
Tetsuro
T
Matsuoka
Department of Biomedical Informatics, Division of Health Sciences, Osaka University Graduate School of Medicine.
Kento
K
Kayama
Department of Biomedical Informatics, Division of Health Sciences, Osaka University Graduate School of Medicine.
Sumire
S
Onishi
Department of Biomedical Informatics, Division of Health Sciences, Osaka University Graduate School of Medicine.
Natsumi
N
Matsuo
Department of Biomedical Informatics, Division of Health Sciences, Osaka University Graduate School of Medicine.
Shinji
S
Kihara
D052242:Adiponectin / Q000097:blood*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D003324:Coronary Artery Disease / Q000097:blood* / Q000000981:diagnostic imaging; D055316:Cystatin C / Q000097:blood*; D005355:Fibrosis; D057809:HEK293 Cells; D006801:Humans; D008055:Lipids / Q000032:analysis; D008297:Male; D008875:Middle Aged; D046912:Multiprotein Complexes / Q000097:blood; D015999:Multivariate Analysis; D009336:Necrosis; D058226:Plaque, Atherosclerotic / Q000097:blood* / Q000737:chemistry / Q000000981:diagnostic imaging
C499918:ADIPOQ protein, human; D052242:Adiponectin; D015415:Biomarkers; C525030:CST3 protein, human; D055316:Cystatin C; D008055:Lipids; D046912:Multiprotein Complexes
Adiponectin; Atherosclerosis; Coronary artery disease; Cystatin C; Plaque