Yue P, Massie B M, Simpson P C, Long C S
Cardiovascular Research Institute, University of California, San Francisco, California 94143, USA.
Am J Physiol. 1998 Jul;275(1):H250-8. doi: 10.1152/ajpheart.1998.275.1.H250.
Growing evidence suggests that cardiac nonmyocyte cells may play an important regulatory role in the response to myocardial overload and injury via altered expression of paracrine products, such as cytokines and growth factors, but information concerning the cell-specific changes in the expression of these substances in heart-failure models is limited. Therefore, cardiac nonmyocytes were isolated from rats 1 day and 1 and 6 wk after left coronary artery ligation with resulting hemodynamic evidence of heart failure and in sham-operated control animals. mRNAs for tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, IL-6, transforming growth factors (TGF)-beta1 and TGF-beta3, and type I and type III collagen were measured by Northern analyses. The temporal and quantitative relationships between the expression of these cytokines and collagen and myocyte hypertrophy were determined. mRNA expression of IL-1beta was increased by 1.3-fold at 1 day and 1 wk, and expression of TNF-alpha, IL-1beta, IL-6, TGF-beta1, and TGF-beta3 were increased by 1.4- to 2.1-fold at the 1-wk time point before returning toward baseline at 6 wk. There were significant correlations between the expression of these cytokines and the expression of types I and III collagen, which also peaked at 1 wk. Myocyte hypertrophy was seen first at 6 wk. These observations are consistent with a hypothesis that nonmyocyte cells play a regulatory role in the extracellular matrix changes during postinfarction remodeling and highlight the importance of examining cell-specific changes in gene expression and elucidating the role of cell-to-cell interactions within the myocardium.
越来越多的证据表明，心脏非心肌细胞可能通过旁分泌产物（如细胞因子和生长因子）表达的改变，在心肌负荷过重和损伤的反应中发挥重要的调节作用，但关于这些物质在心力衰竭模型中细胞特异性表达变化的信息有限。因此，从左冠状动脉结扎术后1天、1周和6周的大鼠中分离出心脏非心肌细胞，这些大鼠出现了心力衰竭的血流动力学证据，同时还选取了假手术对照动物。通过Northern分析测定肿瘤坏死因子-α（TNF-α）、白细胞介素（IL）-1β、IL-6、转化生长因子（TGF）-β1和TGF-β3以及I型和III型胶原蛋白的mRNA。确定了这些细胞因子和胶原蛋白的表达与心肌细胞肥大之间的时间和定量关系。IL-1β的mRNA表达在1天和1周时增加了1.3倍，TNF-α、IL-1β、IL-6、TGF-β1和TGF-β3的表达在1周时间点增加了1.4至2.1倍，然后在6周时恢复到基线水平。这些细胞因子的表达与I型和III型胶原蛋白的表达之间存在显著相关性，I型和III型胶原蛋白的表达也在1周时达到峰值。心肌细胞肥大最早在6周时出现。这些观察结果与一种假设一致，即非心肌细胞在心肌梗死后重塑过程中的细胞外基质变化中起调节作用，并强调了检查基因表达的细胞特异性变化以及阐明心肌内细胞间相互作用作用的重要性。
