Gene expression signals involved in ischemic injury, extracellular matrix composition and fibrosis defined by global mRNA profiling of the human left ventricular myocardium
Gene expression signals involved in ischemic injury, extracellular matrix composition and fibrosis defined by global mRNA profiling of the human left ventricular myocardium
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DOI：
10.1016/j.yjmcc.2006.12.016
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发表时间：
2007-04-01
影响因子：
5
通讯作者：
Hansson, Goran K.
中科院分区：
文献类型：
--
作者：
Gabrielsen, Anders;Lawler, Patrick R.;Hansson, Goran K.
人左心室心肌整体mRNA表达谱确定的缺血性损伤、细胞外基质组成和纤维化相关基因表达信号急性和慢性心肌缺血转化为缺血性心肌病特征的机制目前尚未解决。我们假设这种翻译与急性和慢性炎症过程中特定基因表达程序的改变有关。对心肌的慢性缺血性损伤。通过Affymetrix HG_U133 A GeneChip（R）对33个样本进行全球mRNA表达谱分析，对6名接受冠状动脉旁路移植术的患者在急性和慢性缺血期间的非衰竭人类左心室心肌进行了分析。结果证实了14例患者的实时定量RT-PCR和组织学和免疫组化分析的支持。急性缺血引起急性炎症反应，包括IL-6，IL-8，MCPA，VCAM-1和CYR-61，与正常心肌相比，慢性缺血心肌中IL-6和IL-8的增加减弱。慢性缺血心肌中存在结缔组织生长因子（CTGF）的高mRNA表达，CTGF与参与细胞外基质重塑的特定基因（例如血小板反应蛋白4、I型胶原α 2、多功能蛋白聚糖、adlican、潜伏转化生长因子β结合蛋白2和纤连蛋白）的mRNA表达之间高度相关。总之，急性炎症诱导（如IL-8，IL-6，VCAM-1和MCP-1）和急性时相CCN家族基因与基质相互作用的影响（CYR-61）可能在急性缺血发作和慢性心肌重塑之间的耦合中发挥重要作用。此外，研究结果支持CTGF信号传导在慢性冠状动脉疾病的慢性细胞外基质重塑中的重要作用。(c)2007年爱思唯尔公司All rights reserved.
Gene expression signals involved in ischemic injury, extracellular matrix composition and fibrosis defined by global mRNA profiling of the human left ventricular myocardium. The mechanism(s) by which acute and chronic myocardial ischemia translate into the characteristic features of ischemic cardiomyopathy is unresolved at present. We hypothesized that such translation relates to modification of specific gene expression programs during acute and. chronic ischemic insults to the myocardium. Global mRNA expression profiles by Affymetrix HG_U133A GeneChip (R) analysis on 33 samples was performed on non-failing human left ventricular myocardium- during acute and chronic ischemia in 6 patients undergoing coronary artery by-pass grafting. Results were confirmed by real-time quantitative RT-PCR in 14 patients and supported by histology and immunohistochemistry analyses. Acute ischemia elicited an acute inflammatory response including IL-6, IL-8, MCPA, VCAM-1 and CYR-61 with an attenuated increase of IL-6 and IL-8 in chronic ischemic myocardium compared to normal myocardium. High mRNA expression of connective tissue growth factor (CTGF) was present in chronic ischemic myocardium with a high degree of correlation between CTGF and mRNA expression of specific genes (e.g. thrombospondin 4, collagen type I alpha 2, versican, adlican, latent transforming growth factor beta binding protein 2 and fibronectin) involved in extracellular matrix remodelling. In conclusion, acute inflammatory induction (e.g. IL-8, IL-6, VCAM-1 and MCP-1) and an acute phase CCN family gene with effects on matrix interactions (CYR-61) might play important roles in the coupling between acute ischemic episodes and chronic myocardial remodelling. In addition, the findings support an important role of CTGF signalling in chronic extracellular matrix remodelling in chronic coronary artery disease. (c) 2007 Elsevier Inc. All rights reserved.