Laviades C, Varo N, Fernández J, Mayor G, Gil M J, Monreal I, Díez J
Division of Nephrology, San Jorge General Hospital, Huesca, Spain.
Circulation. 1998 Aug 11;98(6):535-40. doi: 10.1161/01.cir.98.6.535.
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.
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.
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.
本研究旨在调查原发性高血压患者中I型胶原降解是否发生改变，以及这种改变是否与血清中I型胶原降解的基质金属蛋白酶途径紊乱有关。该研究的第二个目的是评估高血压患者中I型胶原降解的血清标志物与左心室肥厚之间是否存在某种关联。
我们测定了37例未经治疗的原发性高血压患者和23例血压正常的对照者血清中I型胶原羧基末端肽（CITP）（作为细胞外I型胶原降解的标志物）、总基质金属蛋白酶-1（MMP-1，即胶原酶）、总金属蛋白酶组织抑制剂1（TIMP-1）以及MMP-1/TIMP-1复合物的浓度。游离MMP-1和游离TIMP-1的血清浓度分别通过从总MMP-1和总TIMP-1的值中减去MMP-1/TIMP-1复合物的值来计算。在26例高血压患者接受血管紧张素转换酶抑制剂赖诺普利治疗1年后重复进行测量。与血压正常者相比，高血压患者的基线游离MMP-1降低（P<0.001），基线游离TIMP-1升高（P<0.001）。两组受试者的CITP基线值未观察到显著差异。与无基线左心室肥厚的高血压患者相比，有基线左心室肥厚的高血压患者的游离MMP-1值较低（P<0.01），CITP值较低（P<0.05），游离TIMP-1值较高（P<0.001）。接受治疗的患者游离MMP-1升高（P<0.001），游离TIMP-1降低（P<0.05）。此外，与血压正常的受试者相比，接受治疗的高血压患者血清CITP升高（P<0.05）。
这些发现表明，原发性高血压患者中I型胶原的全身细胞外降解受到抑制，用赖诺普利治疗可使其恢复正常。I型胶原降解受抑制可能会促进高血压患者（即左心室肥厚患者）的器官纤维化。
