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Published on: September 26, 2018
Effect of MMP-2 deficiency on atherosclerotic lesion formation in apoE-deficient mice
Masafumi Kuzuya1, Kae Nakamura, Takeshi Sasaki
1Department of Geriatrics, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan. kuzuya@med.nagoya-u.ac.jp
Objective:
Although it has been reported that matrix metalloproteinase (MMP)-2 is a major proteinase in atherosclerotic plaque lesions, there is no direct evidence of the role of MMP-2 in atherosclerotic lesion formation. In the present study we determined the role of MMP-2 in atherosclerosis plaque development using apolipoprotein E-deficient (apoE(-/-)) mice.
Methods And Results:
To generate MMP-2-deficient, apoE-deficient mice (MMP-2(-/-):apoE(-/-)), MMP-2(-/-) mice were crossed with apoE(-/-) mice. After 8 weeks of feeding with a lipid-rich diet, morphological and biochemical studies of the aortic sinus and arch were conducted. A significant reduction of the atherosclerotic plaque in the aortic sinus and arch with the decrease in smooth muscle cell-positive area was observed in MMP-2(-/-):apoE(-/-) mice compared with that of MMP-2(+/+):apoE(-/-) mice. Macrophage- and collagen-positive areas were less in aortic sinus but not in aortic arch in MMP-2(-/-):apoE(-/-) mice. There was no difference of MMP-9 mRNA expression in the plaque lesion between the 2 genotypes. A much lower level of mRNA expression of TIMP-1 and TIMP-2 was detected in the atherosclerotic plaque lesions of MMP-2(-/-):apoE(-/-) mice than in those of MMP-2(+/+):apoE(-/-) mice.
Conclusions:
MMP-2 contributes to the development of atherosclerosis in apoE(-/-) mice.
Insights
Matrix metalloproteinase (MMP)-2 plays a key role in atherosclerosis plaque development. MMP-2 deficiency significantly reduced atherosclerotic lesions in apolipoprotein E-deficient mice, indicating its contribution to the disease.
Area of Science:
- Cardiovascular Biology
- Molecular Medicine
- Atherosclerosis Research
Background:
- Matrix metalloproteinase (MMP)-2 is implicated in atherosclerotic plaque pathogenesis.
- Direct evidence for MMP-2's role in lesion formation is lacking.
Purpose of the Study:
- To investigate the specific role of MMP-2 in the development of atherosclerosis.
- To utilize apolipoprotein E-deficient (apoE(-/-)) mice as a model system.
Main Methods:
- Generated MMP-2-deficient, apoE-deficient (MMP-2(-/-):apoE(-/-)) mice by crossing MMP-2(-/-) with apoE(-/-) mice.
- Fed mice a lipid-rich diet for 8 weeks.
- Conducted morphological and biochemical analyses of the aortic sinus and arch.
Main Results:
- MMP-2 deficiency significantly reduced atherosclerotic plaque size in the aortic sinus and arch.
- Observed decreased smooth muscle cell-positive areas in MMP-2 deficient mice.
- Found lower expression of TIMP-1 and TIMP-2 mRNA in atherosclerotic lesions of MMP-2 deficient mice.
Conclusions:
- MMP-2 is a significant contributor to atherosclerosis development in apoE(-/-) mice.
- Targeting MMP-2 may offer therapeutic potential for atherosclerosis.
