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(Hypertension. 1999;33:116-123.)
© 1999 American Heart Association, Inc.
Scientific Contributions |
Increased Expression of Matrix Metalloproteinase-2 in the Thickened Intima of Aged Rats
From the Laboratory of Cardiovascular Science, National Institute on Aging, National Institutes of Health, Baltimore, Md (A.L., J.F., E.G.L.), and Division of Cardiology, Emory University School of Medicine, Atlanta, Ga (Z.S.G.). Dr Li is now with Megabios Corporation, Burlingame, Calif.
Correspondence to Edward G. Lakatta, MD, Laboratory of Cardiovascular Science, Gerontology Research Center, 5600 Nathan Shock Dr, Baltimore, MD 21224.
Abstract—To characterize
remodeling of elastic arteries with aging and to investigate its
potential mechanisms, matrix metalloproteinase-2 (MMP-2), intracellular
adhesive molecule-1 (ICAM-1), transforming growth factor-ß
(TGF-ß), and fibronectin protein levels were measured in
the aortas of young adult (6 months) and aged (30 months) Fischer
344XBN rats. At 30 versus 6 months, the thickness of the intima was
5-fold greater and contained marked increases in TGF-ß and ICAM-1,
and fibronectin expression was enhanced throughout the aortic wall.
Total MMP-2 protein (Western blot) of 30-month-old rats was increased
8-fold over that of 6-month-old rats (0.166±0.032 versus 0.020±0.006;
P<0.01), and staining and activity were regionally
localized to the intima, often near breaks in the internal elastic
membrane and lamellae. Early passage, explanted smooth muscle cells
(SMC) from aged aorta secreted more MMP-2 than those from young aorta;
while basal MMP-2 production did not differ with age, after
stimulation with cytokines (interleukin-1, tumor necrosis
factor-
, or TGF-ß, 10 ng/mL each for 24 hours), MMP-2
production in SMC from 30-month-old rats increased to levels
greater than those in 6-month-old rats. Thus, enhanced
expression of TGF-ß, MMP-2, and ICAM-1 in the thickened vascular
intima of aged rats may in part be produced by exaggerated SMC
responses to cytokines and may have potential roles in intimal
remodeling with aging.
Key Words: intimal thickening • aging • matrix metalloproteinase-2 • cytokines • cells, vascular smooth muscle
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