Negative association between serum levels of matrix metalloproteinases-2 and -9 and aortic stiffness in healthy adults.

BACKGROUND

Arterial stiffness is a marker of cardiovascular disease and independent predictor of cardiovascular risk. Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases that degrade components of the extracellular matrix, which is an important determinant of the arterial elastic properties. This study sought to investigate the association between MMP-2 and MMP-9 (gelatinase A and B respectively) and arterial stiffness in healthy human subjects.

METHODS

A total of 213 apparently healthy subjects (mean age 41 years, range 18 to 60, 141 males and 72 females) were studied. Carotid-femoral pulse wave velocity (PWV) and aortic augmentation index (AIx) were measured as indices of aortic stiffness and wave reflections respectively. Associations with serum levels of total MMP-2, total MMP-9 and high-sensitivity C-reactive protein (hsCRP) were evaluated with multiple regression models.

RESULTS

In these models, PWV exhibited a significant negative association with both MMP-2 (standardized b=-0.177, P=0.003) and MMP-9 (b=-0.122, P=0.032), after controlling for potential confounding factors such as age, gender, blood pressure, heart rate, body-mass index, smoking habits (pack-years), blood glucose, total cholesterol, and level of subclinical inflammation expressed by hsCRP (adjusted R2 of models 0.352 and 0.338 respectively). On the other hand, no relationship between MMP-2 or MMP-9 and AIx was found.

CONCLUSIONS

Circulating MMP-2 and MMP-9 are inversely associated with large artery stiffness but not with wave reflections in healthy persons. This finding implies that these gelatinases may have a possible role in the determination of arterial function and has potential implications for their involvement in the pathophysiology of cardiovascular diseases.