Ji-Hoon Choa,1, Inyoul Leea,1, Rasha Hammamiehb,1, Kai Wanga,1, David Baxtera, Kelsey Scherlera, Alton Etheridgea, Alena Kulchenkoa, Aarti Gautamb, Seid Muhieb, Nabarun Chakrabortyb, David J. Galasc, Marti Jettb, and Leroy Hooda,2
aInstitute for Systems Biology, Seattle, WA 98109;
bIntegrative Systems Biology, US Army Center for Environmental Health Research, Fort Detrick, MD 21702; and
cPacific Northwest Diabetes Research Institute, Seattle, WA 98122
Posttraumatic stress disorder (PTSD) is a common condition induced by life-threatening stress, such as that experienced by soldiers under battlefield conditions. Other than the commonly recognized behavioral and psychological dysfunction, epidemiological studies have also revealed that PTSD patients have a higher risk of other diseases, such as cardiovascular disorders. Using a PTSD mouse model, we investigated the longitudinal transcriptomic changes in heart tissues after the exposure to stress through intimidation. Our results revealed acute heart injury associated with the traumatic experience, reflecting the underlying biological injury processes of the immune response, extracellular matrix remodeling, epithelial-to-mesenchymal cell transitions, and cell proliferation. Whether this type of injury has any long-term effects on heart function is yet to be determined. The differing responses to stress leading to acute heart injury in different inbred strains of mice also suggest that this response has a genetic as well as an environmental component. Accordingly, the results from this study suggest a molecular basis for the observed higher risk of cardiovascular disorders in PTSD patients, which raises the likelihood of cardiac dysfunction induced by long-term stress exposures.
systems biology, transcriptome, microRNA
1J.-H.C., I.L., R.H., and K.W. contributed equally to this work.
2To whom correspondence should be addressed.
Author contributions: I.L., R.H., K.W., D.J.G., M.J., and L.H. designed research; J.-H.C., I.L., R.H., K.W., D.B., K.S., A.E., A.K., A.G., S.M., and N.C. performed research; J.-H.C. contributed new reagents/analytic tools; J.-H.C., I.L., R.H., K.W., A.E., and L.H. analyzed data; and J.-H.C., I.L., K.W., A.E., D.J.G., and L.H. wrote the paper.