TY - JOUR
T1 - Variation in the human matrix metalloproteinase-9 gene is associated with arterial stiffness in healthy individuals
AU - Yasmin,
AU - McEniery, Carmel M.
AU - O'Shaughnessy, Kevin M.
AU - Harnett, Patrick
AU - Arshad, Asif
AU - Wallace, Sharon
AU - Maki-Petaja, Kaisa
AU - McDonnell, Barry
AU - Ashby, Mike J.
AU - Brown, John
AU - Cockcroft, John R.
AU - Wilkinson, Ian B.
PY - 2006/5/18
Y1 - 2006/5/18
N2 - BACKGROUND - Arterial stiffness is an important determinant of cardiovascular risk. Elastin is the main elastic component of the arterial wall and can be degraded by a number of enzymes including serine proteases and matrix metalloproteinases (MMPs). Serum MMP-9 levels correlate with arterial stiffness and predict cardiovascular risk. Polymorphisms in the MMP-9 gene are also associated with large artery function in subjects with coronary artery disease. Therefore, we investigated the influence of known MMP-9 (-1562C>T, R279Q) polymorphisms on arterial stiffness in a large cohort of healthy individuals (n=865). METHODS AND RESULTS - Aortic pulse wave velocity (PWV) and augmentation index were assessed. Supine blood pressure, biochemical markers, MMP-9 levels, and serum elastase activity (SEA) were also determined. Genomic DNA was extracted and genotyping performed. Aortic PWV, serum MMP-9, and SEA were higher in carriers of the rare alleles for the -1562C>T and R279Q polymorphisms. These polymorphisms were also associated with aortic PWV after correction for other confounding factors. Stepwise regression models with known or likely determinants of arterial stiffness revealed that ≈60% of the variability in aortic PWV was attributable to age, mean arterial pressure, and genetic variants (P<0.001). CONCLUSIONS - We have demonstrated for the first time that aortic stiffness and elastase activity are influenced by MMP-9 gene polymorphisms. This suggests that the genetic variation in this protein may be involved in the process of large artery stiffening.
AB - BACKGROUND - Arterial stiffness is an important determinant of cardiovascular risk. Elastin is the main elastic component of the arterial wall and can be degraded by a number of enzymes including serine proteases and matrix metalloproteinases (MMPs). Serum MMP-9 levels correlate with arterial stiffness and predict cardiovascular risk. Polymorphisms in the MMP-9 gene are also associated with large artery function in subjects with coronary artery disease. Therefore, we investigated the influence of known MMP-9 (-1562C>T, R279Q) polymorphisms on arterial stiffness in a large cohort of healthy individuals (n=865). METHODS AND RESULTS - Aortic pulse wave velocity (PWV) and augmentation index were assessed. Supine blood pressure, biochemical markers, MMP-9 levels, and serum elastase activity (SEA) were also determined. Genomic DNA was extracted and genotyping performed. Aortic PWV, serum MMP-9, and SEA were higher in carriers of the rare alleles for the -1562C>T and R279Q polymorphisms. These polymorphisms were also associated with aortic PWV after correction for other confounding factors. Stepwise regression models with known or likely determinants of arterial stiffness revealed that ≈60% of the variability in aortic PWV was attributable to age, mean arterial pressure, and genetic variants (P<0.001). CONCLUSIONS - We have demonstrated for the first time that aortic stiffness and elastase activity are influenced by MMP-9 gene polymorphisms. This suggests that the genetic variation in this protein may be involved in the process of large artery stiffening.
KW - Aortic pulse wave velocity
KW - Augmentation index
KW - MMP-9 gene polymorphisms
KW - MMP-9 levels
KW - Serum elastase activity
UR - http://www.scopus.com/inward/record.url?scp=33746814986&partnerID=8YFLogxK
U2 - 10.1161/01.ATV.0000227717.46157.32
DO - 10.1161/01.ATV.0000227717.46157.32
M3 - Article
C2 - 16709939
AN - SCOPUS:33746814986
SN - 1079-5642
VL - 26
SP - 1799
EP - 1805
JO - Arteriosclerosis, thrombosis, and vascular biology
JF - Arteriosclerosis, thrombosis, and vascular biology
IS - 8
ER -
