Plasma tissue inhibitor of metalloproteinase-1 levels are elevated in essential hypertension and related to left ventricular hypertrophy

Abstract

Background: Essential hypertensive patients have an increased heart and arterial collagen concentration. Increased collagen synthesis can be assessed using procollagen III N peptide (PIIINP) and reduced collagen degradation measured using tissue inhibitor of metalloproteinase-1 (TIMP-1). Methods: Plasma TIMP-1 and PIIINP levels were measured in 31 patients with essential hypertension and in 17 normotensive control subjects. The hypertensive patients were either treatment naive ( n = 18) or had been without treatment for 1 month ( n = 13). Both groups of patients were screened to exclude other fibrotic diseases. Results: In the hypertensive patients, TIMP-1 levels were significantly ( P < .0002) elevated (median 380 ng/mL, range 160 to 1560 ng/mL) compared with those of the normotensive control subjects (median 178 ng/mL, range 99 to 330 ng/mL). In hypertensive subjects who had never received antihypertensive therapy there were significant correlations between TIMP-1 and left ventricular posterior wall thickness in diastole (LVPWd) (r = 0.58) ( P < .02) and left ventricular mass index (r = 0.58) ( P < .02). There was no difference in PIIINP levels (mean ± 2 SD) between the hypertensive (0.56 U/mL ± 0.3) and normotensive groups (0.52 U/mL ± 0.2). Conclusions: The increased tissue collagen III levels found in the heart and vessels of hypertensive patients is due to a reduction in collagen degradation because of high TIMP-1 levels, rather than an increase in synthesis of collagen type III. The tissue source of this TIMP-1 is unclear.