ABNORMALITIES OF THE EXTRACELLULAR DEGRADATION OF COLLAGEN TYPE-I IN ESSENTIAL-HYPERTENSION

Background-This study was designed to investigate whether collagen typ e I degradation is altered in patients with essential hypertension and whether this alteration could be related to disturbances in the serum matrix metalloproteinase pathway of collagen degradation. A second ai m of the study was to assess whether some relation exists between seru m markers of collagen type I degradation and left ventricular hypertro phy in hypertensive patients. Methods and Results-We measured serum co ncentrations of carboxy-terminal telopeptide of collagen type I (CITP) as a marker of extracellular collagen type I degradation, of total ma trix metalloproteinase-1 (MMP-1), or collagenase, of total tissue inhi bitor of metalloproteinases 1 (TIMP-1), and of MMP-1/TIMP-1 complex in 37 patients with never-treated essential hypertension and in 23 normo tensive control subjects. Serum concentrations of free MMP-1 and free TIMP-1 were calculated by subtracting the values of MMP-1/TIMP-1 compl ex from the values of total MMP-1 and total TIMP-1, respectively. Meas urements were repeated in 26 hypertensive patients after 1 year of tre atment with the ACE inhibitor lisinopril. Baseline free MMP-1 was decr eased (P < 0.001) and baseline free TIMP-1 was increased (P < 0.001) i n hypertensives compared with normotensives. No significant difference s were observed in the baseline values of CITP between the 2 groups of subjects. Hypertensive patients with baseline left ventricular hypert rophy exhibited lower values of free MMP-1 (P < 0.01) and CITP (P < 0. 05) and higher (P < 0.001) values of free TIMP-1 than hypertensive pat ients without baseline left ventricular hypertrophy. Treated patients attained an increase (P < 0.001) in free MMP-1 and a decrease (P < 0.0 5) in free TIMP-1. In addition, serum CITP was increased (P < 0.05) in treated hypertensives compared with normotensive subjects. Conclusion s-These findings suggest that systemic extracellular degradation of co llagen type I is depressed in patients with essential hypertension and can be normalized by treatment with lisinopril. A depressed degradati on of collagen type I may facilitate organ fibrosis in hypertensive pa tients, namely, in those with left ventricular hypertrophy.