Role of Matrix Metalloproteinase-2 in the Development of Atherosclerosis among Patients with Coronary Artery Disease

Table 4

Summary of the findings of the selected studies.

	Study design and subject’s characteristics	Mean age (years)	Methods and MMPs measured	MMP-2 level in atherosclerotic CAD	NOS score
Mogharrabi et al.; [33]	Case–control, double-blind, randomized clinical trial.; 70 patients with CAD (40%–50% stenosis) were randomly assigned into two groups: (i) nanocurcumin group (given nanomicelle 80 mg/day); (ii) control group (given placebo); Treatment was given for 3 months	>18 years old	The activity and expression of MMP-2 and MMP-9 in the serum were measured using RT–PCR and zymography analysis	MMP-2 mean relative gelatinase activity was significantly decreased in CAD patients treated with curcumin compared with the placebo group ()	7
Sai et al. [34]	Case–control clinical trial.; 56 patients with AMI were randomly divided into: (i) study group (28 patients; 15 men and 13 women): given 20 mg rosuvastatin and 2.5 mg benazepril daily for 3 months.; (ii) control group (28 patients; 14 men and 14 women): given 20 mg rosuvastatin daily for 3 months.; 30 healthy volunteers were assigned as normal controls (18 men and 12 women)	Study group: 53 ± 12 years old; Control group: 54 ± 0.8 years old; Normal control: 51 ± 1.2 years old	Serum levels of MMP-2, MMP-9, and leukotriene B4 pre- and posttreatment were measured using ELISA	Serum levels of MMP-2 were significantly higher in AMI patients compared with the healthy subjects ().; Serum levels of MMP-2 were significantly decreased in AMI patients treated with both benazepril and rosuvastatin compared with rosuvastatin alone ()	8
Li et al. [35]	Case–control study; 80 patients with acute coronary syndrome: (i) acute group (40 patients; 19 male and 21 female, 26 AMI patients and 14 UAP patients, course of disease ranged from 1 to 6 years); (ii) stable group (40 patients; 18 male and 22 female, 25 AMI patients and 15 UAP patients. course of disease ranged from 2 to 8 years); 40 healthy subjects (control group)	Acute group (37–73 years; mean age: 53.27 ± 1.45 years); Stable group (39–71 years; mean age: 53.04 ± 1.38 years); Control group; (37–68 years; mean age: 52.85 ± 1.46 years)	Serum MMP-2 levels were measured using ELISA	MMP-2 levels were significantly higher: (i) in the acute and stable groups compared with the control group (); (ii) in the acute group compared with the stable group (); (iii) in the AMI patients compared with the UAP patients ()	9
Murashov et al. [36]	Cross-sectional study; 68 men with coronary atherosclerosis who underwent coronary bypass surgery with endarterectomy	46–79 years old	MMP-2 expression in the stable (n = 21) and unstable (n = 31) atherosclerotic plaque in the coronary arteries was determined using immunohistochemistry (IHC)	Expression of MMP-2 in the unstable atherosclerotic plaque was 7.8 times higher in comparison with the stable atherosclerotic plaque ().; MMP-2 was mostly expressed in the cytoplasm of foamy macrophages in the atheromatous core and in the caps of unstable plaque with lipid erosions	4
Murashov et al. [37]	Cross-sectional study; 33 men with occlusive coronary atherosclerosis who underwent coronary bypass surgery with endarterectomy	62.5 ± 10.9 years	MMP-2 expression was measured using IHC in different types of unstable coronary artery plaques, namely necrotic-degenerative type (64%), lipid type (23%), and inflammatory-erosive type (13%)	No significant difference in MMP-2 expression among the three different types of unstable atherosclerotic plaque, suggesting that accumulation of MMP-2 was present in all types of unstable plaque	5
Melin et al. [38]	Cross-sectional study; 268 Type 1 diabetes (TID) patients with CVD, depression, thyroid disease, hypertension, and hyperlipidemia	18–59 years old	Plasma levels of MMP-2, MMP-14, TIMP-2, and TIMP-3 were analyzed by ELISA	MMP-2 and CVD were independently associated with high levels of MMP-14 in T1D patients	5
Malkani et al. [39]	Case–control study; 200 Pakistani subjects; (i) 100 patients with coronary atherosclerosis; (ii) 100 healthy controls	NS	Genomic DNA was extracted from blood samples and subjected to RFLP-PCR analysis for two SNPs of the MMP-2 gene (rs 243865 and rs 243866)	Both allelic and genotype frequencies of rs243865 were higher in atherosclerosis patients than the healthy controls (); Only allelic frequency of rs243866 was higher in atherosclerosis patients than the healthy controls (); Haplotype analysis indicated that CA, CG, and TA haplotypes of the MMP-2 gene were significantly connected with atherosclerosis ()	7
Owolabi et al. [40]	Cohort study; 64 subjects with AMI and stable CAD were divided into two main groups: (i) stable CAD (n = 15); (ii) acute MI (n = 49), which was further divided into atherothrombotic MI (n = 22) and non atherothrombotic MI (n = 12)	>18 years old	Plasma MMP-2 levels were measured using multiplex immunoassay at two main time points: (i) acute phase (at the start of cardiac catheterization and 6 hr post catheterization); (ii) quiescent phase (at 3 months follow-up after acute phase)	No significant difference in MMP-2 levels between acute MI vs. stable CAD, and atherothrombotic vs. nonatherothrombotic MI at any time point	9

AMI, acute myocardial infarction; CAD, coronary artery disease; CVD, cardiovascular disease; ELISA, enzyme-linked immunosorbent assay; MI, myocardial infarction; MMP, matrix metalloproteinase; NS, not stated; RT–PCR, reverse transcription–polymerase chain reaction; RFLP–PCR, restriction fragment length polymorphismpolymerase chain reaction; TIMP, tissue inhibitor of matrix metalloproteinase,; UAP = unstable angina pectoris.