Tozzi Rossana, Palladini Giuseppina, Fallarini Silvia, Nano Rosanna, Gatti Chiara, Presotto Cristina, Schiavone Antonio, Micheletti Rosella, Ferrari Patrizia, Fogari Roberto, Perlini Stefano
Clinica Medica II, Fondazione IRCCS San Matteo, University of Pavia, Pavia, Italy.
Am J Hypertens. 2007 Jun;20(6):663-9. doi: 10.1016/j.amjhyper.2007.01.016.
During the transition of pressure overload hypertrophy (POH) to heart failure (HF) there is intense interstitial cardiac remodeling, characterized by a complex balance between collagen deposition and degradation by matrix metalloproteases (MMPs). This study was aimed at investigating the process of cardiac remodeling during the different phases of the transition of POH to HF.
Guinea pigs underwent thoracic descending aortic banding or sham operation. Twelve weeks after surgery, left-ventricular (LV) end-diastolic internal dimension and ventricular systolic pressure were measured by combined M-mode echocardiography and micromanometer cathetherization. The MMP activity, tissue-specific MMP inhibitors (TIMPs), and collagen fraction were evaluated in LV tissue samples by zymography, ELISA, and computer-aided analysis, respectively.
Banded animals were divided by lung weight values into either compensated left-ventricular hypertrophy (LVH) or HF groups, as compared with sham-operated controls. All HF animals exhibited a restrictive pattern of Doppler transmitral inflow, indicative of diastolic dysfunction, and developed lung congestion. Compensated LVH was associated with increased MMP-2 activity, which was blunted after transition to HF, at a time when TIMP-2 levels and collagen deposition were increased.
The cardiac remodeling process that accompanies the development of POH is a phase-dependent process associated with progressive deterioration of cardiac function.
在压力超负荷肥大（POH）向心力衰竭（HF）转变的过程中，存在强烈的心脏间质重塑，其特征是胶原蛋白沉积与基质金属蛋白酶（MMPs）降解之间的复杂平衡。本研究旨在调查POH向HF转变不同阶段的心脏重塑过程。
豚鼠接受胸降主动脉缩窄术或假手术。术后12周，通过M型超声心动图和微测压导管插入术联合测量左心室（LV）舒张末期内径和心室收缩压。分别通过酶谱法、酶联免疫吸附测定（ELISA）和计算机辅助分析评估LV组织样本中的MMP活性、组织特异性MMP抑制剂（TIMPs）和胶原蛋白含量。
与假手术对照组相比，根据肺重量值将缩窄动物分为代偿性左心室肥大（LVH）组或HF组。所有HF动物均表现出多普勒二尖瓣流入的限制性模式，提示舒张功能障碍，并出现肺充血。代偿性LVH与MMP-2活性增加有关，在转变为HF后，MMP-2活性减弱，此时TIMP-2水平和胶原蛋白沉积增加。
POH发展过程中伴随的心脏重塑过程是一个与心脏功能逐渐恶化相关的阶段依赖性过程。
