Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, Ohio Northern University, Ada, OH, USA.
Department of Pharmacology and Cancer Biology, Duke University, Durham, NC, USA.
Stress. 2020 Mar;23(2):125-135. doi: 10.1080/10253890.2019.1641081. Epub 2019 Jul 26.
People who are exposed to life-threatening trauma are at risk of developing posttraumatic stress disorder (PTSD). In addition to psychological manifestations, PTSD is associated with an increased risk of myocardial infarction, arrhythmias, hypertension, and other cardiovascular problems. We previously reported that rats exposed to a predator-based model of PTSD develop myocardial hypersensitivity to ischemic injury. This study characterized cardiac changes in histology and gene expression in rats exposed this model. Male rats were subjected to two cat exposures (separated by a period of 10 d) and daily cage-mate changes for 31 d. Control rats were not exposed to the cat or cage-mate changes. Ventricular tissue was analyzed by RNA sequencing, western blotting, histology, and immunohistochemistry. Multifocal lesions characterized by necrosis, mononuclear cell infiltration, and collagen deposition were observed in hearts from all stressed rats but none of the control rats. Gene expression analysis identified clusters of upregulated genes associated with endothelial to mesenchymal transition, endothelial migration, mesenchyme differentiation, and extracellular matrix remodeling in hearts from stressed rats. Consistent with endothelial to mesenchymal transition, rats from stressed hearts exhibited increased expression of α-smooth muscle actin (a myofibroblast marker) and a decrease in the number of CD31 positive endothelial cells. These data provide evidence that predator-based stress induces myocardial lesions and reprograming of cardiac gene expression. These changes may underlie the myocardial hypersensitivity to ischemia observed in these animals. This rat model may provide a useful tool for investigating the cardiac impact of PTSD and other forms of chronic psychological stress.Chronic predator stress induces the formation of myocardial lesions characterized by necrosis, collagen deposition, and mononuclear cell infiltration. This is accompanied by changes in gene expression and histology that are indicative of cardiac remodeling. These changes may underlie the increased risk of arrhythmias, myocardial infarction, and other cardiac pathologies in people who have PTSD or other forms of chronic stress.
暴露于危及生命的创伤的人有患创伤后应激障碍（PTSD）的风险。除了心理表现外，PTSD 还与心肌梗死、心律失常、高血压和其他心血管问题的风险增加有关。我们之前报道过，暴露于基于捕食者的 PTSD 模型的大鼠会发展出对缺血性损伤的心肌超敏性。本研究描述了暴露于该模型的大鼠的心脏组织学和基因表达变化。雄性大鼠接受了两次猫暴露（间隔 10 天）和每日笼伴变化 31 天。对照大鼠未暴露于猫或笼伴变化。通过 RNA 测序、Western blot、组织学和免疫组织化学分析心室组织。从所有应激大鼠的心脏中观察到多灶性病变，特征为坏死、单核细胞浸润和胶原沉积，但对照大鼠均无。基因表达分析确定了与应激大鼠心脏中内皮到间充质转化、内皮迁移、间充质分化和细胞外基质重塑相关的上调基因簇。与内皮到间充质转化一致，应激大鼠心脏中α-平滑肌肌动蛋白（成纤维肌细胞标志物）的表达增加，而 CD31 阳性内皮细胞的数量减少。这些数据提供了证据表明，基于捕食者的应激会导致心肌损伤和心脏基因表达的重新编程。这些变化可能是这些动物观察到的缺血性心肌超敏反应的基础。这种大鼠模型可能为研究 PTSD 和其他形式的慢性心理应激对心脏的影响提供有用的工具。慢性捕食者应激会导致以坏死、胶原沉积和单核细胞浸润为特征的心肌病变的形成。这伴随着基因表达和组织学的变化，表明心脏重塑。这些变化可能是 PTSD 或其他形式的慢性应激患者心律失常、心肌梗死和其他心脏病理的风险增加的基础。
