Matrix metalloproteinases/tissue inhibitors of metalloproteinases - Relationship between changes in proteolytic determinants of matrix composition and structural, functional, and clinical manifestations of hypertensive heart disease
Matrix metalloproteinases/tissue inhibitors of metalloproteinases - Relationship between changes in proteolytic determinants of matrix composition and structural, functional, and clinical manifestations of hypertensive heart disease
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DOI：
10.1161/circulationaha.105.573865
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发表时间：
2006-05-02
期刊：
影响因子：
37.8
通讯作者：
Zile, MR
中科院分区：
文献类型：
--
作者：
Ahmed, SH;Clark, LL;Zile, MR
背景 - 慢性高血压可能导致左心室 (LV) 重塑、心功能改变以及慢性心力衰竭 (CHF) 的发展。已知在高血压中发生的细胞外基质（ECM）组成的变化被认为与这些结构、功能和临床结果存在因果关系。然而，ECM 组成的决定因素，例如 ECM 蛋白酶（基质金属蛋白酶 [MMP] 及其组织抑制剂 [TIMP]）之间的平衡，在高血压心脏病中是否发生改变尚不清楚。方法和结果 - 获得 103 名受试者的血浆 MMP-2、-9 和 -13 值、TIMP-1 和 -2 值以及多普勒超声心动图图像 分为 4 组：(1) 无心血管疾病证据的参考受试者 (CTL)，(2) 血压受控且无左心室肥厚的高血压 (HTN) 受试者，(3) 血压受控且左心室肥厚 (HTN + LVH) 但无 CHF 的高血压受试者，以及 (4) 血压受控、LVH 和 CHF 的高血压受试者 (HTN + LVH) + 瑞士法郎）。与CTL相比，HTN患者的任何MMP或TIMP均无明显变化。 HTN + LVH 患者的 MMP-2 和 MMP-13 值降低，MMP-9 值升高。只有 HTN + LVH + CHF 患者的 TIMP-1 值升高。 TIMP-1 水平 > 1200 ng/mL 可预测 CHF。结论 - 患有高血压但 LV 结构和功能正常的患者具有正常的 MMP/TIMP 谱。 MMP 谱的变化有利于减少 ECM 降解，与 LVH 和舒张功能障碍相关。 TIMP-1 水平升高预示着 CHF 的存在。尽管这些发现应该在更大规模的前瞻性研究中得到证实，但这些数据确实表明 MMP/TIMP 平衡的变化可能在高血压心脏病的结构、功能和临床表现中发挥重要作用。
Background - Chronic hypertension may cause left ventricular (LV) remodeling, alterations in cardiac function, and the development of chronic heart failure (CHF). Changes in the composition of the extracellular matrix (ECM) known to occur in hypertension are believed to be causally related to these structural, functional, and clinical outcomes. However, whether the determinants of ECM composition, such as the balance between ECM proteases (matrix metalloproteinases [MMPs] and their tissue inhibitors [TIMPs]), are altered in hypertensive heart disease is unknown.Methods and Results - Plasma MMP-2, -9, and -13 values, TIMP-1 and -2 values, and Doppler echocardiography images were obtained for 103 subjects divided into 4 groups: (1) reference subjects (CTL) with no evidence of cardiovascular disease, (2) hypertensive (HTN) subjects with controlled blood pressure and no LV hypertrophy, (3) hypertensive subjects with controlled blood pressure and with LV hypertrophy (HTN + LVH) but no CHF, and (4) hypertensive subjects with controlled blood pressure, LVH, and CHF (HTN + LVH + CHF). Compared with CTL, patients with HTN had no significant changes in any MMP or TIMP. Patients with HTN + LVH had decreased MMP-2 and MMP-13 values and increased MMP-9 values. Only patients with HTN + LVH + CHF had increased TIMP-1 values. A TIMP-1 level > 1200 ng/mL was predictive of CHF.Conclusions - Patients with hypertension but normal LV structure and function had normal MMP/TIMP profiles. Changes in MMP profiles that favor decreased ECM degradation were associated with LVH and diastolic dysfunction. An increased TIMP-1 level predicted the presence of CHF. Although these findings should be confirmed in a larger prospective study, these data do suggest that changes in the MMP/TIMP balance may play an important role in the structural, functional, and clinical manifestations of hypertensive heart disease.