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原发性高血压患者血清基质金属蛋白酶-9和金属蛋白酶组织抑制因子-1水平及降压治疗的影响

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

作者信息

Onal Ibrahim Koral, Altun Bulent, Onal Eda Demir, Kirkpantur Alper, Gul Oz Serife, Turgan Cetin

机构信息

Hacettepe University Medical School, Ankara, Turkey.

出版信息

Eur J Intern Med. 2009 Jul;20(4):369-72. doi: 10.1016/j.ejim.2008.10.003. Epub 2008 Nov 28.

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.

摘要

背景

基质金属蛋白酶是一类蛋白水解酶,被认为参与了高血压靶器官疾病发展过程中的细胞外基质积聚。本研究旨在比较高血压患者与血压正常个体的血清基质金属蛋白酶(MMP)-9和金属蛋白酶组织抑制剂(TIMP)-1水平,并探究降压治疗对血清酶水平的影响。

方法

33例1期原发性高血压患者和16例年龄及性别匹配的对照者纳入本研究。在高血压组进行为期3个月的降压治疗(17例患者服用坎地沙坦8mg/天,16例患者服用赖诺普利10mg/天)前后,评估血清MMP-9和TIMP-1水平。

结果

高血压组治疗前血清MMP-9水平较高(p=0.309),而血清TIMP-1水平较低(p=0.296)。降压治疗后,血清MMP-9水平降低(p<0.001),TIMP-1水平升高(p=0.022)。

结论

在高血压患者中,MMP-9活性增加可能导致弹性蛋白相对于胶原蛋白的降解增加以及非弹性化,而TIMP-1活性降低可能导致交联不良、不成熟和不稳定的纤维降解产物积聚,从而导致胶原蛋白的错误沉积。我们的研究对于揭示MMP酶系统在高血压靶器官疾病发病机制中的作用具有重要意义。

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