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.
McNulty
Marie
M
Department of Pharmacology and Therapeutics, Trinity College, Dublin, Ireland. mcnultm@tcd.ie
Spiers
Paul
P
McGovern
Eilis
E
Feely
John
J
D000368:Aged; D000375:Aging / Q000378:metabolism*; D001011:Aorta / Q000201:enzymology* / Q000378:metabolism; D015153:Blotting, Western; D005260:Female; D006801:Humans; D008297:Male; D008323:Mammary Arteries / Q000201:enzymology / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008875:Middle Aged; D014018:Tissue Distribution; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism
D019716:Tissue Inhibitor of Metalloproteinase-2; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9