Carver W, Nagpal M L, Nachtigal M, Borg T K, Terracio L
Department of Anatomy, Cell Biology, and Neurosciences, University of South Carolina School of Medicine, Columbia 29208.
Circ Res. 1991 Jul;69(1):116-22. doi: 10.1161/01.res.69.1.116.
The cardiac extracellular matrix, composed predominantly of collagenous fibers, forms a stress-tolerant network that facilitates the distribution of forces generated in the heart and provides for proper alignment of cardiac myocytes. Although considerable information exists regarding the morphological organization of the heart extracellular matrix, little is known about the regulation of the synthesis and accumulation of extracellular matrix components. A potentially significant factor in the cardiovascular system is mechanical stimulation including changes in physical tension and pressure. We recently have developed an in vitro model system to elucidate the effects of mechanical stretch on isolated populations of heart cells. In the present study, we have used biochemical and molecular biological techniques to analyze changes in collagen synthesis by cardiac fibroblasts in response to mechanical stretch. These studies show that the ratio of collagen type III to collagen type I increases in mechanically stretched cells. They also show that type III collagen mRNA levels are increased in response to cyclic mechanical stretch for durations as short as 12 hours. Type I collagen mRNA levels were not found to change under the stretch conditions used in this study. Our results emphasize the potential regulatory role of mechanical stimulation in the expression of specific genes in the heart and support previous studies indicating this to be an intriguing in vitro model of cardiac hypertrophy.
心脏细胞外基质主要由胶原纤维组成,形成一个抗压网络,有助于心脏产生的力的分布,并使心肌细胞正确排列。尽管关于心脏细胞外基质的形态组织已有相当多的信息,但对于细胞外基质成分的合成和积累的调节却知之甚少。心血管系统中一个潜在的重要因素是机械刺激,包括物理张力和压力的变化。我们最近开发了一种体外模型系统,以阐明机械拉伸对分离的心脏细胞群体的影响。在本研究中,我们使用生化和分子生物学技术来分析心脏成纤维细胞在机械拉伸响应下胶原合成的变化。这些研究表明,在机械拉伸的细胞中,III型胶原与I型胶原的比例增加。它们还表明,III型胶原mRNA水平在短至12小时的周期性机械拉伸后会升高。在本研究使用的拉伸条件下,未发现I型胶原mRNA水平发生变化。我们的结果强调了机械刺激在心脏特定基因表达中的潜在调节作用,并支持先前的研究,表明这是一个有趣的心脏肥大体外模型。