title: Molecular Mechanisms of Stress-Induced Myocardial Injury in a Rat Model Simulating Posttraumatic Stress Disorder.
abstract: Posttraumatic stress disorder (PTSD) is an independent risk factor for cardiovascular diseases. This study investigated the molecular mechanisms underlying myocardial injury induced by simulated PTSD.
  
  
  
  Sprague-Dawley rats were randomly divided into two groups: control group (n = 18) and PTSD group (n = 30). The PTSD model was replicated using the single prolonged stress (SPS) method. On the 14th day poststress, the apoptotic cells in myocardium were assessed using both TUNEL method and transmission electron microscopy; the protein levels of the endoplasmic reticulum stress (ERS) molecules were measured by using Western blotting analysis.
  
  
  
  Exposure to SPS resulted in characteristic morphologic changes of apoptosis in cardiomyocytes assessed by transmission electron microscopy. Moreover, TUNEL staining was also indicative of the elevated apoptosis rate of cardiomyocytes from the SPS rats (30.69% versus 7.26%, p < .001). Simulated PTSD also induced ERS in myocardium, demonstrated by up-regulation of protein levels of glucose-regulated protein 78 (0.64 versus 0.26, p = .017), calreticulin (p = .040), and CCAAT/enhancer-binding protein-homologous protein (0.95 versus 0.43, p = .047), phosphorylation of protein kinase RNA-like ER kinase (p = .003), and caspase 12 activation (0.30 versus 0.06, p < .001) in myocardium from the SPS rats. The ratio of Bcl-2 to Bax decreased significantly in myocardium from the SPS rats (p = .005).
  
  
  
  The ERS-related apoptosis mediated by the protein kinase RNA-like ER kinase/CCAAT/enhancer-binding protein-homologous protein and caspase 12 pathways may be associated with myocardial injury in a rat model simulating PTSD. This study may advance our understanding of how PTSD contributes to myocardial injury on a molecular level.
authors.affiliation: From the Department of Pathophysiology (Liu, Xu, Tao, Song, Li D, Li Y, Guo, Liu), Chinese PLA General Hospital, Beijing, China; and State Key Laboratory of Kidney Disease (Xiuhua), Chinese PLA General Hospital, Beijing, China.
authors.forename: Mi
authors.initials: M
authors.lastname: Liu
authors.forename: Feifei
authors.initials: F
authors.lastname: Xu
authors.forename: Tianqi
authors.initials: T
authors.lastname: Tao
authors.forename: Dandan
authors.initials: D
authors.lastname: Song
authors.forename: Dong
authors.initials: D
authors.lastname: Li
authors.forename: Yuzhen
authors.initials: Y
authors.lastname: Li
authors.forename: Yucheng
authors.initials: Y
authors.lastname: Guo
authors.forename: Xiuhua
authors.initials: X
authors.lastname: Liu
mesh_terms: D000818:Animals; D017209:Apoptosis; D022762:CCAAT-Enhancer-Binding Proteins / Q000378:metabolism; D053454:Caspase 12 / Q000378:metabolism; D004195:Disease Models, Animal; D059865:Endoplasmic Reticulum Stress; D006335:Heart Injuries / Q000209:etiology / Q000378:metabolism*; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D013313:Stress Disorders, Post-Traumatic / Q000150:complications / Q000378:metabolism*; D019892:eIF-2 Kinase / Q000378:metabolism
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; D053454:Caspase 12; D019892:eIF-2 Kinase