Identification, characterization, and gene expression profiling of endotoxin-induced myocarditis
Year: 2003
Type: article
Abstract: In septic shock, reversible cardiac dysfunction starts within 24 h. Myocardial depressant factors are thought to cause myocyte dysfunction, resulting in alterations of intrinsic cardiac function. Nitric oxide is a myocardial depressant factor candidate. Here we identify endotoxin-induced myocarditis (EIM) a previously uncharacterized pathophysiological entity. Features of EIM include differential patterns of inducible NO synthase (NOS2) mRNA induction in the left (LV) and right (RV) ventricles during the systemic response inflammatory syndrome (SIRS) and the presence of myocarditis with focal areas of aseptic necrosis in the RV 24 h after SIRS induction. Even though clinical data lead to the presumption of myocardial injury in sepsis, the underlying pathophysiological mechanisms have not been previously elucidated. Gene expression profiling was used to test the hypothesis of differential LV and RV responses in EIM, and revealed novel patterns of qualitative and quantitative expansion of transcription. Those genes are novel targets for drug development in SIRS and sepsis. Our results demonstrate spatial and temporal heterogeneity of myocardial responses in EIM. These findings justify the design of treatments to ameliorate tissue injury in the RV. Because the complexity of the inflammatory response increases substantially as time elapses, we suggest a stepwise and multitarget therapeutic approach for SIRS and sepsis. Our findings can help identify innate immune pathways that could become targets for immunotherapy in the treatment of disease caused by potential bioterrorism agents.
Authors: Ma-Li Wong, Fiona O'Kirwan, Nadia Khan, Jonas Hannestad, Kwok H. Wu, David Elashoff, Gregory Lawson, Philip W. Gold, Samuel M. McCann, Julio Licinio
Institution: University of California, Los Angeles
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funders: National Alliance for Research on Schizophrenia and Depression, National Institutes of Health, University of Illinois at Urbana-Champaign, University of California, Los Angeles, National Heart, Lung, and Blood Institute, National Institute of Mental Health, National Human Genome Research Institute, National Institute of General Medical Sciences, National Institute of Diabetes and Digestive and Kidney Diseases, National Center for Research Resources
Awards: G1179106364, G1182606348, G1466907488, G155212455, UCLA Mentored Clinical Pharmacology Research Scholar Pr*, UCLA GRADUATE TRAINING PROGRAM IN TRANSITIONAL INVESTIGA, Depression/Metabolic Syndrome in Mexican-American Women., UCLA Pharmacogenetics and Pharmacogenomics Research Grp*, CNS transcription modulation in peripheral inflammation, G3563942022, Developing Educational Approaches for Mexican-Americans, G4261709681, G444342022, Pharmacogenetics of Antidepressant Drugs, Endocrine Effects of Human Leptin Replacement, General Clinical Research Center, G4729432281, Clinical Neuroendocrinology of Leptin, G6190901191, G701510884
OpenAlex ID: W2001013005