Tan Jing, Hua Qi, Xing Xiurong, Wen Jing, Liu Rongkun, Yang Zheng
Department of Cardiology, Xuanwu Hospital, Capital Medical University, Beijing, PR China.
Hypertens Res. 2007 Oct;30(10):959-63. doi: 10.1291/hypres.30.959.
The extracellular matrix is vital for maintaining tissue integrity, and the matrix metalloproteinases/tissue inhibitors of metalloproteinases (MMPs/TIMPs) system is involved in the regulation of extracellular matrix metabolism. Extracellular matrix turnover plays an important role in the change of large arterial mechanical properties in hypertension. However, the association of the metalloproteinase-9/tissue inhibitor of metalloproteinase-1 (MMP-9/TIMP-1) system and arterial stiffness is not straightforward and existing data are rather limited. Our objective is to explore the impact of the MMP-9/TIMP-1 system on large arterial stiffness in patients with essential hypertension. An automatic pulse wave velocity (PWV) measuring system was used to examine carotid-femoral PWV (CFPWV) and carotid-radial PWV (CRPWV) as the parameters reflecting central elastic large arterial and peripheral muscular medium-sized arterial elasticity, respectively; and serum MMP-9 and TIMP-1 levels, along with a number of other established biomarkers, were measured by enzyme-linked immunosorbent assay (ELISA) in 202 essential hypertensive patients and 54 age and gender-matched control subjects. Compared with the control subjects, hypertensive patients exhibited higher levels of MMP-9 (p=0.001) and TIMP-1 (p=0.002). Spearman's correlation analysis showed that serum levels of MMP-9 (p=0.014) and TIMP-1 (p=0.005) were significantly and positively correlated with CFPWV in hypertensive patients. A stepwise multiple regressive analysis demonstrated that age, systolic blood pressure, heart rate and TIMP-1 were independent predictors of CFPWV in patients with essential hypertension (adjusted r2=0.458). In conclusion, our results imply that the MMP-9/TIMP-1 system may play an important role in the determination of arterial function, and these findings may have implications for the involvement of MMP-9/TIMP-1 system in the pathophysiology of cardiovascular disease.
细胞外基质对于维持组织完整性至关重要，基质金属蛋白酶/金属蛋白酶组织抑制剂（MMPs/TIMPs）系统参与细胞外基质代谢的调节。细胞外基质周转在高血压患者大动脉力学特性变化中起重要作用。然而，金属蛋白酶-9/金属蛋白酶组织抑制剂-1（MMP-9/TIMP-1）系统与动脉僵硬度之间的关联并不直接，现有数据相当有限。我们的目的是探讨MMP-9/TIMP-1系统对原发性高血压患者大动脉僵硬度的影响。使用自动脉搏波速度（PWV）测量系统分别检测颈股PWV（CFPWV）和颈桡PWV（CRPWV），作为反映中心弹性大动脉和外周肌肉型中动脉弹性的参数；采用酶联免疫吸附测定（ELISA）法检测202例原发性高血压患者和54例年龄及性别匹配的对照者血清MMP-9和TIMP-1水平以及其他一些已确定的生物标志物。与对照者相比，高血压患者的MMP-9（p = 0.001）和TIMP-1（p = 0.002）水平较高。Spearman相关性分析显示，高血压患者血清MMP-9（p = 0.014）和TIMP-1（p = 0.005）水平与CFPWV显著正相关。逐步多元回归分析表明，年龄、收缩压、心率和TIMP-1是原发性高血压患者CFPWV的独立预测因素（调整后r2 = 0.458）。总之，我们的结果表明，MMP-9/TIMP-1系统可能在动脉功能的决定中起重要作用，这些发现可能对MMP-9/TIMP-1系统参与心血管疾病的病理生理学具有启示意义。
