Abnormalities of the extracellular degradation of collagen type I in essential hypertension
Abnormalities of the extracellular degradation of collagen type I in essential hypertension
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DOI：
10.1161/01.cir.98.6.535
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发表时间：
1998-08-11
期刊：
影响因子：
37.8
通讯作者：
Díez, J
中科院分区：
文献类型：
--
作者：
Laviades, C;Varo, N;Díez, J
背景：本研究旨在探讨原发性高血压患者I型胶原降解是否发生改变，以及这种改变是否与胶原降解的血清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血清I型胶原降解标志物与左心室肥厚之间是否存在某种关系。方法与结果：我们检测了37例从未治疗过的原发性高血压患者和23例血压正常者的血清I型胶原羧基末端末端肽（CITP）浓度，总基质金属蛋白酶-1 （MMP-1）或胶原酶，总组织金属蛋白酶-1抑制剂（TIMP-1）和MMP-1/TIMP-1复合物的浓度。用总MMP-1和总TIMP-1分别减去MMP-1/TIMP-1复合物的值，计算血清游离MMP-1和游离TIMP-1的浓度。26例高血压患者在使用ACE抑制剂赖诺普利治疗1年后重复测量。与正常血压组相比，高血压组基线游离MMP-1降低（P < 0.001），基线游离TIMP-1升高（P < 0.001）。两组受试者的ctp基线值无显著差异。伴有左室肥厚的高血压患者游离MMP-1 （P < 0.01）、CITP （P < 0.05）低于无左室肥厚的高血压患者，游离TIMP-1 （P < 0.001）高于无左室肥厚的高血压患者。治疗后患者游离MMP-1升高（P < 0.001），游离TIMP-1降低（P < 0.05）。此外，高血压治疗组血清CITP较正常组升高（P < 0.05）。结论：这些发现提示原发性高血压患者I型胶原的全身细胞外降解受到抑制，并可通过赖诺普利治疗使其正常化。I型胶原蛋白降解降低可能促进高血压患者，即左心室肥厚患者的器官纤维化。
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.