Bonnema D Dirk, Webb Carson S, Pennington Weems R, Stroud Robert E, Leonardi Amy E, Clark Leslie L, McClure Catherine D, Finklea Laura, Spinale Francis G, Zile Michael R
Division of Cardiology, Department of Medicine, Medical University of South Carolina and RHJ Department of Veterans Affairs Medical Center, Charleston, South Carolina 29425, USA.
J Card Fail. 2007 Sep;13(7):530-40. doi: 10.1016/j.cardfail.2007.04.010.
The mechanisms causing age-dependent changes in left ventricular (LV) structure and function are not completely understood. Matrix metalloproteinase (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) constitute one important proteolytic pathway affecting LV remodeling. However, whether these determinants of extracellular matrix (ECM) composition change as a function of age has not been examined in an aging population free of clinically significant cardiovascular disease.
Subjects (n = 77, age 20-90 years) with no evidence of cardiovascular disease underwent echocardiography and measurement of plasma MMP-2, 7, 8, and 9 and TIMP-1, 2, and 4 (enzyme-linked immunosorbent assay). As subject age increased, volume/mass ratio decreased and mitral E/A ratio decreased. As subject age increased, MMP-2 increased (from 1188 +/- 99 ng/mL to 1507 +/- 76 ng/mL), MMP-7 increased (from 1.2 +/- 0.1 ng/mL to 3.1 +/- 0.6 ng/mL), MMP-9 decreased (from 29 +/- 7 ng/mL to 8 +/- 2 ng/mL), and TIMP-1, 2, and 4 increased (from 728 +/- 46 ng/mL to 1093 +/- 73 ng/mL, from 34 +/- 5 ng/mL to 53 +/- 6 ng/mL, and from 1.26 +/- 0.22 ng/mL to 2.34 +/- 0.30 ng/mL, respectively) (all P < .05). There were significant correlations between decreased LV volume/mass and E/A ratio and increased MMP-7 and TIMP-1 and 4.
MMPs and TIMPs changed as a function of age in the absence of clinically significant cardiovascular disease. These age-dependent alterations in MMP and TIMP profiles favor ECM accumulation and were associated with concentric remodeling and decreased LV diastolic function. Because of these age-dependent changes in this proteolytic system, the superimposition of disease processes such as myocardial infarction or hypertensive heart disease in the older subject may result in different myocardial ECM remodeling than that seen in a younger subject.
导致左心室（LV）结构和功能随年龄变化的机制尚未完全明确。基质金属蛋白酶（MMPs）和金属蛋白酶组织抑制剂（TIMPs）构成影响左心室重塑的一条重要蛋白水解途径。然而，在无临床显著心血管疾病的老年人群中，这些细胞外基质（ECM）组成的决定因素是否随年龄变化尚未得到研究。
对77名（年龄20 - 90岁）无心血管疾病证据的受试者进行超声心动图检查，并测量血浆MMP - 2、7、8和9以及TIMP - 1、2和4（酶联免疫吸附测定）。随着受试者年龄增加，容积/质量比降低，二尖瓣E/A比值降低。随着受试者年龄增加，MMP - 2升高（从1188±99 ng/mL升至1507±76 ng/mL），MMP - 7升高（从1.2±0.1 ng/mL升至3.1±0.6 ng/mL），MMP - 9降低（从29±7 ng/mL降至8±2 ng/mL），TIMP - 1、2和4升高（分别从728±46 ng/mL升至1093±73 ng/mL，从34±5 ng/mL升至53±6 ng/mL，从1.26±0.22 ng/mL升至2.34±0.30 ng/mL）（均P <.05）。左心室容积/质量和E/A比值降低与MMP - 7以及TIMP - 1和4升高之间存在显著相关性。
在无临床显著心血管疾病的情况下，MMPs和TIMPs随年龄变化。MMP和TIMP谱的这些年龄依赖性改变有利于ECM积聚，并与向心性重塑和左心室舒张功能降低相关。由于该蛋白水解系统存在这些年龄依赖性变化，老年受试者中诸如心肌梗死或高血压性心脏病等疾病过程的叠加可能导致与年轻受试者不同的心肌ECM重塑。
