Myocardial immediate early gene activation after cardiopulmonary bypass with cardiac ischemia-reperfusion
Myocardial immediate early gene activation after cardiopulmonary bypass with cardiac ischemia-reperfusion
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DOI：
10.1016/s0003-4975(01)03303-3
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发表时间：
2002-01-01
影响因子：
4.6
通讯作者：
Neufeld, EJ
中科院分区：
文献类型：
--
作者：
Nelson, DP;Wechsler, SB;Neufeld, EJ
背景体外循环术后的炎症过程伴随着各种炎症介质基因表达的改变。为了分析心肌缺血-再灌注后的差异基因表达，使用减法杂交来发现TIS 7/PC 4的诱导，TIS 7/PC 4是迄今为止在心脏中未观察到的立即早期基因。这促使表征的相关立即早期基因c-fos和c-jun，北方分析和原位杂交在人和羊心肌进行心肺转流心肌缺血。为了比较，我们分析了诱导型一氧化氮合酶（iNOS）的表达，这需要精氨酸激活，导致“延迟”的响应。在体外循环缺血再灌注心肌，c-fos，c-jun，和TIS 7/PC 4诱导，而iNOS转录检测不到。原位杂交显示c-fos和c-jun的表达模式明显不同，心肌c-fos表达呈弥漫性、均匀性，而c-jun表达呈斑片状，有明显的局灶性分布。心肌缺血的心脏搭桥术快速诱导立即早期基因TIS 7/PC 4（通过减法杂交发现）和c-fos和c-jun（转录调节因子AP-1的前体）。即刻早期基因可能有助于体外循环后炎症介质的激活，其组织表达模式的差异，如c-fos和c-jun所观察到的，可能调节其对下游基因激活的影响。(C)2002年由胸外科医师协会出版。
Background. The inflammatory process after cardiopulmonary bypass is accompanied by alterations in gene expression for various inflammatory mediators.Methods. To analyze differential gene expression after myocardial ischemia-reperfusion, subtraction hybridization was used to discover induction of TIS7/PC4, an immediate early gene heretofore not observed in the heart. This prompted characterization of the related immediate early genes c-fos and c-jun, by Northern analysis and in situ hybridization in human and lamb myocardium subjected to cardiopulmonary bypass with myocardial ischemia. For comparison, we analyzed expression of inducible nitric oxide synthase (iNOS), which requires cytokine-activation, resulting in a "delayed" response.Results. In ischemic-reperfused myocardium at endcardiopulmonary bypass, c-fos, c-jun, and TIS7/PC4 were induced, whereas iNOS transcripts were undetectable. Expression patterns of c-fos and c-jun by in situ hybridization were markedly different; myocardial c-fos expression was diffuse and homogeneous, whereas c-jun expression was patchy with areas of intense focal localization.Conclusions. Cardiopulmonary bypass with myocardial ischemia rapidly induces the immediate early genes TIS7/PC4 (discovered by subtraction hybridization), and c-fos and c-jun (precursors to the transcriptional regulator AP-1). Immediate early genes presumably contribute to activation of inflammatory mediators after cardiopulmonary bypass and differences in their tissue expression patterns, as observed for c-fos and c-jun, presumably modulate their effect upon downstream gene activation. (C) 2002 by The Society of Thoracic Surgeons.