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HERDIN Record #: PCHRD091807050909 Submitted: 19 September 2007

Aging increases aortic MMP-2 activity and angiotensin II in nonhuman primates .

Edward G. Lakatta,
Filipinas F. Natividad,
Gen Takagi,
Stephen F. Vatner,
Ranilo G. Resuello,
Mingyi Wang,
Dorothy E. Vatner,
Kuniya Asai

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To seek evidence that the nonhuman primate arterial wall, as it ages in the absence of atherosclerosis, exhibits alterations in pathways that are involved in the pathogenesis of experimental atherosclerosis, we assessed aortic matrix metalloproteinase-2 (MMP-2) and its regulators, ie, membrane type-1 of matrix metalloproteinase (MT1-MMP) and tissue inhibitor of matrix metalloproteinase-2 (TIMP-2), and the expression of angiotensin II (Ang II), angiotensin-converting enzyme (ACE), and chymase in young (6.4 +/- 0.7 years) and old (20.0 +/- 1.9 years) male monkeys. With advancing age, (1) the intimal thickness increased 3-fold and contained numerous vascular smooth muscle cells and matrix, but no inflammatory cells; (2) the intirnal MMP-2 antibody- staining fraction increased by 80 percent (/><0.01); (3) in situ zymography showed that MMP-2 activity, mainly confined to the intima, increased 3-fold (P<0.01); (4) the MT1-MMP antibody-staining fraction increased by 150 percent (P<0.001), but the TIMP-2 antibody-staining fraction did not significantly change; (5) steady levels of the mRNA-staining fraction (via in situ hybridization) for MMP-2 increased 7-fold, for MT1-MMP increased 9-fold, and for TIMP-2 increased 2-fold (all P<0.001); and (6) intimal Ang II and ACE irnmunofluorescence were increased 5-fold and 5.6-fold, respectively, and colocalized with MMP-2. Thus, age-associated arterial remodeling and the development and progression of experimental atherosclerosis in young animals share common mechanisms, ie, MMP-2 activation and increased Ang II signaling. This might explain, in part, the dramatically exaggerated prevalence and severity of vascular diseases with aging. (Author)

Publication Type
Publication Sub Type
Publication Date
November 2002
LocationLocation CodeAvailable FormatAvailability
Philippine Council for Health Research and Development Library Abstract Print Format