Abnormalities of the extracellular degradation of collagen type I in essential hypertension.
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.


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.
Laviades
C
C
Division of Nephrology, San Jorge General Hospital, Huesca, Spain.
Varo
N
N
Fernández
J
J
Mayor
G
G
Gil
M J
MJ
Monreal
I
I
Díez
J
J
D000328:Adult; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D003094:Collagen / Q000097:blood / Q000378:metabolism*; D017364:Collagenases / Q000097:blood; D004452:Echocardiography; D005110:Extracellular Space / Q000378:metabolism*; D005260:Female; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000188:drug therapy / Q000378:metabolism*; D017379:Hypertrophy, Left Ventricular / Q000000981:diagnostic imaging / Q000188:drug therapy; D017706:Lisinopril / Q000627:therapeutic use; D008297:Male; D020781:Matrix Metalloproteinase 1; D008875:Middle Aged; D009994:Osmolar Concentration; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood
D000806:Angiotensin-Converting Enzyme Inhibitors; D019715:Tissue Inhibitor of Metalloproteinase-1; D003094:Collagen; D017706:Lisinopril; D017364:Collagenases; D020781:Matrix Metalloproteinase 1