Matrix Metalloproteinase-3 Genotype Contributes to Age-Related Aortic Stiffening Through Modulation of Gene and Protein Expression

ABSTRACT—Matrix metalloproteinases (MMPs) include most major constituents of the arterial wall as substrates. A common promotor polymorphism (5A/6A) is associated with differences in MMP-3 (stromelysin-1) activity, and associations with certain forms of vascular disease have been shown. This study i...

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Bibliographic Details
Published in:Circulation research 2003-06, Vol.92 (11), p.1254-1261
Main Authors: Medley, Tanya L, Kingwell, Bronwyn A, Gatzka, Christoph D, Pillay, Prakash, Cole, Timothy J
Format: Article
Language:English
Subjects:
Adult
Aged
Aging
Aorta - physiology
Biological and medical sciences
Blood Pressure
Blood vessels and receptors
Compliance
Fundamental and applied biological sciences. Psychology
Gene Expression Regulation
Genetics of eukaryotes. Biological and molecular evolution
Genotype
Human
Humans
Male
Matrix Metalloproteinase 3 - biosynthesis
Matrix Metalloproteinase 3 - genetics
Middle Aged
Polymorphism, Genetic
Population genetics, reproduction patterns
Regional Blood Flow
RNA, Messenger - biosynthesis
Vertebrates: cardiovascular system
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Summary:ABSTRACT—Matrix metalloproteinases (MMPs) include most major constituents of the arterial wall as substrates. A common promotor polymorphism (5A/6A) is associated with differences in MMP-3 (stromelysin-1) activity, and associations with certain forms of vascular disease have been shown. This study investigated whether the MMP-3 5A/6A promoter polymorphism contributes to age-related large artery stiffening. MMP-3 5A/6A genotype was determined in 203 (135 male) low cardiovascular risk, unmedicated individuals who were divided prospectively into two groups (30 to 60 years, n=126; ≥61 years, n=77). Noninvasive large artery stiffness was measured as ascending aortic input impedance from brachial blood pressure, carotid tonometry, and Doppler ascending aortic blood flow. In the older group, homozygotes had higher aortic input (P
ISSN:0009-7330
1524-4571
DOI:10.1161/01.RES.0000076891.24317.CA