Impact of the metalloproteinase-9/tissue inhibitor of metalloproteinase-1 system on large arterial stiffness in patients with essential hypertension

Abstract

The extracellular matrix is vital for maintaining tissue integrity, and the matrix metalloproteinases/tissue inhibitors of metalloproteinases (MMPs/TIMPs) system is involved in the regulation of extracellular matrix metabolism. Extracellular matrix turnover plays an important role in the change of large arterial mechanical properties in hypertension. However, the association of the metalloproteinase-9/tissue inhibitor of metalloproteinase-1 (MMP-9/TIMP-1) system and arterial stiffness is not straightforward and existing data are rather limited. Our objective is to explore the impact of the MMP-9/TIMP-1 system on large arterial stiffness in patients with essential hypertension. An automatic pulse wave velocity (PWV) measuring system was used to examine carotid-femoral PWV (CFPWV) and carotid-radial PWV (CRPWV) as the parameters reflecting central elastic large arterial and peripheral muscular medium-sized arterial elasticity, respectively; and serum MMP-9 and TIMP-1 levels, along with a number of other established biomarkers, were measured by enzyme-linked immunosorbent assay (ELISA) in 202 essential hypertensive patients and 54 age and gender-matched control subjects. Compared with the control subjects, hypertensive patients exhibited higher levels of MMP-9 (p=0.001) and TIMP-1 (p=0.002). Spearman's correlation analysis showed that serum levels of MMP-9 (p=0.014) and TIMP-1 (p=0.005) were significantly and positively correlated with CFPWV in hypertensive patients. A stepwise multiple regressive analysis demonstrated that age, systolic blood pressure, heart rate and TIMP-1 were independent predictors of CFPWV in patients with essential hypertension (adjusted r2=0.458). In conclusion, our results imply that the MMP-9 /TIMP-1 system may play an important role in the determination of arterial function, and these findings may have implications for the involvement of MMP-9/TIMP-1 system in the pathophysiology of cardiovascular disease.