Table 1.

List of studies showing associations between circulating MMP-9 levels and atherosclerosis.

Author, reference	Study design	Patient populations	Main study findings
Fukuda et al. [19]	Cross-sectional study	47 AMI patients, 23 UAP patients, and 19 SAP patients	Patients with plaque rupture had significantly higher levels of MMP-9 than patients who did not have plaque rupture.
Tan et al. [68]	Human study	116 stroke-free participants	Elevated serum MMP-9 concentration was independently associated with high total carotid artery plaque score, plaque instability, and large IMT value.
Olson et al. [69]	Cross-sectional study	473 61-year-old men	Plasma MMP-9 concentration was higher in men with echolucent femoral plaques, while no similar associations were found for carotid plaques.
Kobayashi et al. [71]	Human study	200 patients with ST elevation ACS and 66 patients with non-ST elevation ACS	MMP-9 levels significantly increased in early ACS than late ACS, while the hs-TnT levels were lower in early ACS than late ACS. Meanwhile, MMP-9 levels were elevated earlier than hs-TnT and had a higher diagnostic value for early ACS.
Tziakas et al. [73]	Human study	18 carotid specimens and serum obtained from 18 patients	MMP-9 levels measured in extracts from the most stenotic area were significantly higher in patients with intraplaque hemorrhage. However, serum levels of MMP-9 showed no difference.
Brunner et al. [77]	Human study	18 SAP patients, 14 UAP/NSTEMI patients, 14 STEMI patients, and 16 healthy controls	Monocytic MMP-9 mRNA levels were increased in patients with UAP/NSTEMI or STEMI compared to the controls and patients with SAP.
Koizumi et al. [81] Kaden et al. [82] Funayama et al. [83]	Human study		Plasma MMP-9 levels were significantly increased in infarct-related artery than those in femoral artery. MMP-9 levels returned to baseline by 1 week after MI.
Inokubo et al. [84]	Human study	29 ACS patients, 9 UAP patients, 17 SAP patients, and 20 control subjects	Plasma MMP-9 levels were significantly increased in coronary circulation, but not in aortic root.
Higo et al. [85]	Human study	23 AMI patients and 10 SAP patients performing percutaneous coronary intervention	Plasma MMP-9 levels were significantly higher in patients with AMI and further increased after percutaneous coronary intervention.
Hamed et al. [86]	Human study	75 ACS patients, 25 SAP patients and 20 healthy participants	Patients with ACS having adverse cardiovascular events had higher levels of MMP-9.
Eldrup et al. [87]	Human study	Followed up 207 patients with > or =50% carotid stenosis initially for a mean of 4.4 years	Elevated MMP-9 was associated with the risk of stroke and cardiovascular death.
Jefferis et al. [88]	Prospective study	368 incident MI patients and 299 incident stroke patients and two controls per case. Follow up for 8 years	Serum MMP-9 was not a strong independent risk marker for MI and stroke.
Garvin et al. [89]	Human study	428 men and 438 women (45-69 years), free of previous coronary events and stroke. Follow up for 8 years	Plasma MMP-9 was independently associated with the risk of first-time CHD.
Welsh et al. [90]	Human study	Followed up 5661 men for 16 years	MMP-9 was unlikely to be a clinically useful biomarker for CHD after adjustment for conventional risk factors (especially smoking).
Eldrup et al. [91]	Human study	Followed up 1090 patients with stable coronary heart disease for 15years	Elevated matrix metalloproteinase-9 had no association with increased risk of unstable angina, MI and death in patients with stable coronary heart disease.

Abbreviations: MMP-9: matrix metalloproteinase-9; MI: myocardial infarction; AMI: acute myocardial infarction; UAP: unstable angina pectoris; SAP: stable angina pectoris; hs-TnT: high sensitivity troponin T; ACS: acute coronary syndrome; STEMI: ST-elevation myocardial infarction; NSTEMI: non-ST segment elevation myocardial infarction; CHD: coronary heart disease.