Department of Anesthesiology, David Geffen School of Medicine, University of California - Los Angeles, Los Angeles, CA 90095, USA.
J Mol Cell Cardiol. 2010 Jul;49(1):88-94. doi: 10.1016/j.yjmcc.2010.01.021. Epub 2010 Feb 17.
Cyclooxygenase-2 (COX-2) is an important mediator of inflammation in stress and disease states. Recent attention has focused on the role of COX-2 in human heart failure and diseases owing to the finding that highly specific COX-2 inhibitors (i.e., Vioxx) increased the risk of myocardial infarction and stroke in chronic users. However, the specific impact of COX-2 expression in the intact heart remains to be determined. We report here the development of a transgenic mouse model, using a loxP-Cre approach, which displays robust COX-2 overexpression and subsequent prostaglandin synthesis specifically in ventricular myocytes. Histological, functional, and molecular analyses showed that ventricular myocyte specific COX-2 overexpression led to cardiac hypertrophy and fetal gene marker activation, but with preserved cardiac function. Therefore, specific induction of COX-2 and prostaglandin in vivo is sufficient to induce compensated hypertrophy and molecular remodeling.
环氧化酶-2（COX-2）是应激和疾病状态下炎症的重要介质。由于发现高度特异性的 COX-2 抑制剂（如 Vioxx）会增加慢性使用者心肌梗死和中风的风险，因此最近人们关注 COX-2 在人类心力衰竭和疾病中的作用。然而，完整心脏中 COX-2 表达的确切影响仍有待确定。我们在这里报告了一种使用 loxP-Cre 方法的转基因小鼠模型的开发，该模型在心室肌细胞中特异性过表达 COX-2 和随后的前列腺素合成。组织学、功能和分子分析表明，心室肌细胞特异性 COX-2 过表达导致心脏肥大和胎儿基因标志物激活，但心脏功能保持不变。因此，体内特异性诱导 COX-2 和前列腺素足以诱导代偿性肥大和分子重塑。
