Elevated level of ADAMTS4 in plasma and peripheral monocytes from patients with acute coronary syndrome.
OBJECTIVE
A recent study shows that ADAMTS4 is expressed in macrophage-rich areas of human atherosclerotic carotid plaques and coronary unstable plaques, suggesting a pathogenic role of ADAMTS4 in the development of acute coronary syndrome (ACS). We investigated (a) whether the expression level of ADAMTS4 in plasma and peripheral blood mononuclear cells was affected; and (b) whether there was a relationship with hs-CRP level and the stability of coronary atherosclerotic plaque in patients with ACS.


METHODS
Our study included 30 normal controls and 120 patients including 40 with stable angina (SA), 50 with unstable angina (UA), and 30 with acute myocardial infarction (AMI). The expression of ADAMTS4 in monocytes was analyzed by RT-PCR and plasma ADAMTS4 level was determined by ELISA. All coronary stenosis with >30% diameter reduction was assessed by angiographic coronary stenosis morphology.


RESULTS
Patients with ACS showed a significant increase of ADAMTS4 (2.7 ± 0.4) expression in monocytes compared with controls (1.1 ± 0.2) and the SA group (1.3 ± 0.2) (P < 0.001). Plasma ADAMTS4 also showed a higher level in ACS patients (100.2 ± 31.6 ng/ml) than in control (47.5 ± 9.0 ng/ml, P < 0.001) and the SA group (54.3 ± 13.2 ng/ml, P < 0.001). Moreover, we found a positive correlation between hs-CRP and ADAMTS4 expression in monocytes as well as in plasma. There was also a positive correlation of ADAMTS4 expression in monocytes and plasma with complex coronary stenosis (r (1) = 0.61, r (2) = 0.57, P < 0.001).


CONCLUSIONS
Patients with ACS showed increased ADAMTS4 expression, which may aggravate the development of atherosclerosis and instability of atherosclerotic plaques. Therefore, the ADAMTS4 expression may be a valuable marker for predicting the severity of ACS.
Zha
Yanping
Y
Department of Cardiology, Provincial Hospital Affiliated to Shandong University, Jinan, China. zhayanping315@126.com
Chen
Yong
Y
Xu
Fayun
F
Zhang
Jie
J
Li
Tian
T
Zhao
Chuanyan
C
Cui
Lianqun
L
D051722:ADAM Proteins / Q000235:genetics / Q000378:metabolism*; D000071121:ADAMTS4 Protein; D054058:Acute Coronary Syndrome / Q000235:genetics / Q000473:pathology*; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D002097:C-Reactive Protein / Q000378:metabolism; D016022:Case-Control Studies; D023921:Coronary Stenosis / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism*; D058226:Plaque, Atherosclerotic / Q000473:pathology*; D011348:Procollagen N-Endopeptidase / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012720:Severity of Illness Index
D015415:Biomarkers; D002097:C-Reactive Protein; D051722:ADAM Proteins; D011348:Procollagen N-Endopeptidase; D000071121:ADAMTS4 Protein; C000603918:ADAMTS4 protein, human