Aging is associated with increased matrix metalloproteinase-2 activity in the human aorta
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Published on: November 18, 2022
Marie McNulty1, Paul Spiers, Eilis McGovern
1Department of Pharmacology and Therapeutics, Trinity College, Dublin, Ireland. mcnultm@tcd.ie
Background:
Aging is a major risk factor for the development of arterial stiffness and vascular disease, and it is related to the upregulation of matrix metalloproteinase-2 (MMP-2) in the aorta of rats and nonhuman primates. This study aimed to determine whether MMP activity in the human vasculature changes with aging. We also assessed regional differences in MMP activity at two locations in the arterial tree, the aorta and the internal mammary artery (IMA).
Methods:
Both MMP-2 and MMP-9 activity in the human aorta and IMA were determined by gelatin zymography and were localized within the tissue using in situ zymography. Tissue inhibitor of metalloproteinase-2 (TIMP-2) levels was determined by Western blot.
Results:
Active MMP-2 (but not pro-MMP-2, pro-MMP-9, or active MMP-9) was positively correlated with age in the human aorta (r = 0.65; P < .001) but not in the IMA. Active MMP-2 and TIMP-2 (but not pro-MMP-2 or pro- or active MMP-9) levels are higher in the aorta than in the IMA (P < .001; P < .05). In the aorta, MMP activity is highest in the intima and is also detectable in the media and adventitia. To a lesser extent, MMP activity is present in all layers of the IMA.
Conclusions:
This study demonstrates that age-related MMP-2 upregulation occurs in the human aorta but not in the IMA.
Insights
Aging increases matrix metalloproteinase-2 (MMP-2) activity in the human aorta, but not the internal mammary artery (IMA). This age-related MMP-2 upregulation in the aorta contributes to vascular disease risk.
Area of Science:
- Vascular Biology
- Aging Research
- Biochemistry
Background:
- Aging is a significant risk factor for arterial stiffness and vascular disease.
- Matrix metalloproteinase-2 (MMP-2) upregulation in the aorta is linked to aging in animal models.
Purpose of the Study:
- To investigate age-related changes in matrix metalloproteinase (MMP) activity within the human vasculature.
- To compare MMP activity in the human aorta versus the internal mammary artery (IMA).
Main Methods:
- Gelatin zymography and in situ zymography were used to assess MMP-2 and MMP-9 activity in human aorta and IMA.
- Western blot analysis determined tissue inhibitor of metalloproteinase-2 (TIMP-2) levels.
Main Results:
- Active MMP-2 levels positively correlated with age in the human aorta (r = 0.65; P < .001), but not in the IMA.
- Higher levels of active MMP-2 and TIMP-2 were found in the aorta compared to the IMA.
- MMP activity was highest in the aortic intima and present in all layers of the IMA.
Conclusions:
- Age-related upregulation of MMP-2 occurs in the human aorta.
- MMP activity in the internal mammary artery does not show age-related changes.
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