Meldrum Daniel R, Wang Meijing, Tsai Ben M, Kher Ajay, Pitcher Jeffrey M, Brown John W, Meldrum Kirstan K
Department of Surgery, Indiana University Medical Center, IB 461, Indianapolis, Indiana 46202, USA.
Front Biosci. 2005 May 1;10:1835-67. doi: 10.2741/1665.
Sex hormones are important modifiers of the acute inflammatory response to injury, an important aspect of myocardial depression and apoptosis following ischemia or endotoxemia. Hemorrhage, trauma, ischemia/reperfusion, burn and sepsis each lead to cardiac dysfunction. Gender has been shown to influence the inflammatory response as well as outcomes following acute injury. The mechanisms by which sex affects the inflammatory response and the outcome to acute injury are being actively investigated. It is now recognized that myocardial inflammation plays a crucial role in I/R-induced myocardial dysfunction. Inflammatory mediators, such as TNF-alpha are produced by cardiomyocytes and contribute to myocardial functional depression and apoptosis. Gender differences in the inflammatory response following burn injury have been demonstrated. However, gender differences in the setting of acute I/R-induced inflammation are unclear. In addition, a critical component of the signal transduction pathway leading to myocardial inflammation is the activation of p38 mitogen-activated protein kinase (MAPK). In other systems, it appears that gender differences exist in the p38 MAPK signaling pathway. The inflammatory response, including the p38 MAPK signaling cascade and expression of proinflammatory cytokines such as TNF-alpha and IL-1beta, may precipitate cardiomyocyte apoptosis following I/R injury. Apoptosis may be an essential component in the pathogenesis of heart failure, and there is evidence that myocyte apoptosis in the failing human heart is markedly lower in women than in men. The prevention of cell death attenuates I/R-induced injury on myocardial anatomy and performance. This review will: 1) examine evidence for gender differences in the outcome to acute injury; 2) explain the myocardial inflammatory response to acute injury; and 3) elucidate the various mechanisms by which gender and sex hormones affect the myocardial response to acute injury.
性激素是对损伤的急性炎症反应的重要调节因子，是缺血或内毒素血症后心肌抑制和细胞凋亡的一个重要方面。出血、创伤、缺血/再灌注、烧伤和脓毒症均会导致心脏功能障碍。性别已被证明会影响急性损伤后的炎症反应以及预后。目前正在积极研究性别影响炎症反应和急性损伤预后的机制。现在人们认识到，心肌炎症在缺血/再灌注诱导的心肌功能障碍中起关键作用。炎症介质，如肿瘤坏死因子-α由心肌细胞产生，并导致心肌功能抑制和细胞凋亡。烧伤后炎症反应中的性别差异已得到证实。然而，急性缺血/再灌注诱导的炎症情况下的性别差异尚不清楚。此外，导致心肌炎症的信号转导通路的一个关键组成部分是p38丝裂原活化蛋白激酶（MAPK）的激活。在其他系统中，p38 MAPK信号通路似乎存在性别差异。炎症反应，包括p38 MAPK信号级联以及促炎细胞因子如肿瘤坏死因子-α和白细胞介素-1β的表达，可能会在缺血/再灌注损伤后促使心肌细胞凋亡。细胞凋亡可能是心力衰竭发病机制中的一个重要组成部分，并且有证据表明，在衰竭的人类心脏中，女性心肌细胞凋亡明显低于男性。预防细胞死亡可减轻缺血/再灌注对心肌结构和功能的损伤。本综述将：1）研究急性损伤预后中性别差异的证据；2）解释心肌对急性损伤的炎症反应；3）阐明性别和性激素影响心肌对急性损伤反应的各种机制。
