From the Divisions of Nephrology (C.L.) and Cardiology (G.M.), San Jorge
General Hospital, Huesca; the Department of Clinical Chemistry, University
Clinic (N.V., J.F., M.J.G., I.M.), and Vascular Pathophysiology Unit, School
of Medicine (J.D.), University of Navarra, Pamplona; and the Department of
Medicine, School of Medicine, University of Zaragoza (J.D.), Spain.
Correspondence to Javier Díez, MD, PhD, Unidad de Fisiopatología Vascular, Facultad de Medicina, C/Irunlarrea s/n, 31080 Pamplona, Spain.
Background—This study was designed
to investigate whether collagen type 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 aim of the
study was to assess whether some relation exists between serum markers
of collagen type I degradation and left ventricular
hypertrophy in hypertensive patients.
Methods and Results—We measured serum concentrations of
carboxy-terminal telopeptide of collagen type I (CITP) as a marker of
extracellular collagen type I degradation, of total matrix
metalloproteinase-1 (MMP-1), or collagenase, of total
tissue inhibitor of metalloproteinases 1 (TIMP-1), and of
MMP-1/TIMP-1 complex in 37 patients with never-treated essential
hypertension and in 23 normotensive control subjects. Serum
concentrations of free MMP-1 and free TIMP-1 were calculated by
subtracting the values of MMP-1/TIMP-1 complex from the values of total
MMP-1 and total TIMP-1, respectively. Measurements were repeated in 26
hypertensive patients after 1 year of treatment with the ACE
inhibitor lisinopril. Baseline free MMP-1 was
decreased (P<0.001) and baseline free TIMP-1 was
increased (P<0.001) in hypertensives compared with
normotensives. No significant differences were observed in the baseline
values of CITP between the 2 groups of subjects. Hypertensive patients
with baseline left ventricular hypertrophy
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 patients without baseline left
ventricular hypertrophy. Treated patients
attained an increase (P<0.001) in free MMP-1 and a
decrease (P<0.05) in free TIMP-1. In addition, serum
CITP was increased (P<0.05) in treated hypertensives
compared with normotensive subjects.
Conclusions—These findings suggest that systemic extracellular
degradation of collagen type I is depressed in patients with essential
hypertension and can be normalized by treatment with
lisinopril. A depressed degradation of collagen type I may
facilitate organ fibrosis in hypertensive patients, namely, in those
with left ventricular hypertrophy.
© 1998 American Heart Association, Inc.
Clinical Investigation and Reports
Abnormalities of the Extracellular Degradation of Collagen Type I in Essential Hypertension
Key Words: collagen • hypertension • metalloproteinases • peptides • remodeling
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