MMP-1 serum levels predict coronary atherosclerosis in humans.
BACKGROUND
Myocardial infarction results as a consequence of atherosclerotic plaque rupture, with plaque stability largely depending on the lesion forming extracellular matrix components. Lipid enriched non-calcified lesions are considered more instable and rupture prone than calcified lesions. Matrix metalloproteinases (MMPs) are extracellular matrix degrading enzymes with plaque destabilisating characteristics which have been implicated in atherogenesis. We therefore hypothesised MMP-1 and MMP-9 serum levels to be associated with non-calcified lesions as determined by CT-angiography in patients with coronary artery disease.


METHODS
260 patients with typical or atypical chest pain underwent dual-source multi-slice CT-angiography (0.6-mm collimation, 330-ms gantry rotation time) to exclude coronary artery stenosis. Atherosclerotic plaques were classified as calcified, mixed or non-calcified.


RESULTS
In multivariable regession analysis, MMP-1 serum levels were associated with total plaque burden (OR: 1.37 (CI: 1.02-1.85); p < 0.05) in a model adjusted for age, sex, BMI, classical cardiovascular risk factors, hsCRP, adiponectin, pericardial fat volume and medication. Specification of plaque morphology revealed significant association of MMP-1 serum levels with non-calcified plaques (OR: 1.16 (CI: 1.0-1.34); p = 0.05) and calcified plaques (OR: 1.22 (CI: 1,03-1.45); p < 0.05) while association with mixed plaques was lost in the fully adjusted model. No associations were found between MMP9 serum levels and total plaque burden or plaque morphology.


CONCLUSIONS
MMP-1 serum levels are associated with total plaque burden but do not allow a specification of plaque morphology.
Lehrke
Michael
M
Department of Internal Medicine II, University of Munich, Munich, Germany. Michael.Lehrke@med.uni-muenchen.de
Greif
Martin
M
Broedl
Uli C
UC
Lebherz
Corinna
C
Laubender
Rüdiger P
RP
Becker
Alexander
A
von Ziegler
Franz
F
Tittus
Janine
J
Reiser
Maximilian
M
Becker
Christoph
C
Göke
Burkhard
B
Steinbeck
Gerhard
G
Leber
Alexander W
AW
Parhofer
Klaus G
KG
D000273:Adipose Tissue / Q000473:pathology; D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use; D000368:Aged; D015415:Biomarkers; D015992:Body Mass Index; D002114:Calcinosis / Q000097:blood / Q000000981:diagnostic imaging; D002637:Chest Pain / Q000209:etiology; D002784:Cholesterol / Q000097:blood; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000097:blood* / Q000175:diagnosis / Q000000981:diagnostic imaging / Q000453:epidemiology; D023921:Coronary Stenosis / Q000097:blood* / Q000175:diagnosis / Q000000981:diagnostic imaging / Q000453:epidemiology; D005260:Female; D006801:Humans; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000097:blood*; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D008875:Middle Aged; D010496:Pericardium / Q000473:pathology; D011237:Predictive Value of Tests; D012307:Risk Factors; D036542:Tomography, Spiral Computed; D014280:Triglycerides / Q000097:blood
D000319:Adrenergic beta-Antagonists; D015415:Biomarkers; D014280:Triglycerides; D002784:Cholesterol; D020780:Matrix Metalloproteinase 9; D020781:Matrix Metalloproteinase 1