Serum levels of MMP-9 and TIMP-1 in primary hypertension and effect of antihypertensive treatment☆

Abstract 

Background

Matrix metalloproteinases, a family of proteolytic enzymes are thought to be involved in extracellular matrix accumulation during development of hypertensive target organ disease. The present study was designed to compare hypertensive patients with normotensive individuals with respect to serum levels of matrix metalloproteinase (MMP)-9 and tissue inhibitor of metalloproteinase (TIMP)-1 and to search for the effect of antihypertensive treatment on the serum enzyme levels.

Methods

Thirty-three patients with stage 1 primary hypertension and sixteen age- and sexmatched control subjects were enrolled into the study. Serum MMP-9 and TIMP-1 levels were assessed in the hypertensive group before and after a 3-month-antihypertensive treatment (candesartan 8 mg/day to 17 patients and lisinopril 10 mg/day to 16 patients).

Results

Pre-treatment serum MMP-9 levels were higher in the hypertensive group (p=0.309) while serum TIMP-1 levels were lower (p=0.296). Serum MMP-9 levels were decreased (p<0.001) and TIMP-1 levels were increased (p=0.022) after the antihypertensive treatment.

Conclusions

In hypertensive patients, increased MMP-9 activity could result in increased degradation of elastin relative to collagen and non-elasticity, while decreased TIMP-1 activity could lead to accumulation of poorly cross-linked, immature and unstable fibril degradation products, which result in misdirected deposition of collagen. Our study is important for revealing the role of the MMP enzyme system in the pathogenesis of hypertensive target organ disease.

Keywords: Matrix metalloproteinases, Hypertension, Renin Angiotensin System