Aging is associated with increased matrix metalloproteinase-2 activity in the human aorta

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.