Mitogen-activated protein kinase pathways and cardiac surgery
Mitogen-activated protein kinase pathways and cardiac surgery
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DOI：
10.1016/j.jtcvs.2003.04.001
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发表时间：
2004-03-01
影响因子：
6
通讯作者：
Sellke, FW
中科院分区：
文献类型：
--
作者：
Khan, TA;Bianchi, C;Sellke, FW
丝裂原激活蛋白激酶是丝氨酸-苏氨酸蛋白激酶，参与对心脏手术重要的几个过程，例如血管通透性、细胞因子产生、血管舒缩功能和再灌注损伤。丝裂原激活蛋白激酶在多种细胞类型中表达，包括心肌细胞、血管内皮细胞和血管平滑肌细胞。丝裂原激活蛋白激酶在细胞信号转导级联中起作用，并被多种刺激激活，包括缺血、剪切应力和血管活性剂。三个主要的丝裂原激活蛋白激酶家族被确定为细胞外信号调节激酶、c-Jun NH2 末端蛋白激酶和 p38 激酶。广泛的研究已经确定了细胞外信号调节激酶、c-Jun NH2 末端蛋白激酶和 p38 激酶在心血管信号转导途径中的作用。这些信号级联的活性可能导致心脏停搏液和体外循环心脏手术后观察到的肺血管通透性增加和心肌再灌注损伤。我们实验室的最新研究结果表明，心肌细胞外信号调节激酶途径活性的改变是由于人类心麻痹-心肺转流引起的。此外，细胞外信号调节激酶活性的这些差异被证明可以介导与心麻痹-心肺旁路相关的冠状动脉微循环功能障碍。由此产生的冠状动脉微循环调节缺陷可能会对器官灌注和功能产生不利影响。随着丝裂原激活蛋白激酶途径的进一步表征，我们开发预防与心脏手术和体外循环相关的发病率的方法的潜力可能会大大提高。
Mitogen-activated protein kinases are serine-threonine protein kinases that are involved in several processes important to cardiac surgery such as vascular permeability, cytokine production, vasomotor function, and reperfusion injury. Mitogen-activated protein kinases are expressed in multiple cell types including cardiomyocytes, vascular endothelial cells, and vascular smooth muscle cells. Mitogen-activated protein kinases function in cellular signal transduction cascades and are activated by a diverse range of stimuli including ischemia, shear stress, and vasoactive agents. Three major mitogen-activated protein kinase families were identified as the extracellular signal-regulated kinases, c-Jun NH2-terminal protein kinases, and p38 kinases. Extensive investigation has established roles for extracellular signal-regulated kinases, c-Jun NH2-terminal protein kinases, and p38 kinases in cardiovascular signal transduction pathways. Activity of these signal cascades may contribute to the increased pulmonary vascular permeability and myocardial reperfusion injury observed after cardiac surgery with cardioplegia and cardiopulmonary bypass. Recent findings from our laboratory suggest that alterations in the activity of myocardial extracellular signal-regulated kinase pathways occur as a result of cardioplegia-cardiopulmonary bypass in humans. In addition, these differences in extracellular signal-regulated kinase activity were shown to mediate coronary microcirculatory dysfunction associated with cardioplegia-cardiopulmonary bypass. The resulting deficit in coronary microcirculatory regulation may potentially lead to detrimental effects on organ perfusion and function. As mitogen-activated protein kinase pathways are further characterized, our potential to develop methods to prevent morbidity associated with cardiac surgery and cardiopulmonary bypass may be greatly improved.