In the February 2014 issue of the Proceedings of the National Academy of Sciences of the USA (PNAS) Ji-Hoon Choa and colleagues from the Institute for Systems Biology, Seattle, WA, USA, used an adapted aggressor-exposed social stress mouse model for PTSD to demonstrate genetically associated stress-induced tissue injuries on peripheral organs, including the heart.
Posttraumatic stress disorder (PTSD) is perhaps the most common psychological disorder as ~7% of the US population suffers, at any given time, from some form of PTSD.
Individuals with PTSD have dysfunctional hypothalamic–pituitary–adrenal (HPA) axis and sympathetic nervous system (SNS) – the two branches of the peripheral stress system – with elevated norepinephrine (NE, noradrenaline) levels in the cerebrospinal fluid and higher NE/cortisol urinary ratios. Importantly, these individuals also have a higher risk of cardiovascular conditions such as hypertension and stroke, with an increased basal heart rate and blood pressure, and elevated blood cholesterol levels.
The first association between ‘PTSD’ and heart conditions was perhaps made by Jacob Mendes Da Costa in 1871 when he described that serious cardiac conditions (cardiomyopathy, heart failure, heart pain, etc.) were probably caused by the extended stress exposures in Civil War soldiers (Da Costa’s syndrome, also known as ‘soldier’s heart’ or ‘irritable heart’ syndrome).
More recently the stress-induced cardiomyopathy, or the ‘Takotsubo’ cardiomyopathy, has been linked to stress-induced inflammation, and particularly catecholamine-induced inflammation that may drive acute symptoms and transiently altered heart functions.
Now, the authors of the PNAS study found that the acute heart injury induced by this experimental PTSD stress model is associated with underlying biological injury processes and alterations of key molecular processes, including an inflammatory response, extracellular matrix remodeling, epithelial-to-mesenchymal transitions (EMTs) and cell proliferation.
Most of the changes in the heart transcriptome occurred after 3 days, but the authors could clearly document some stress-induced effects, such as the up-regulation of a battery of inflammation-related genes, after as little as 1 day of exposure to stress. Of note, the investigators report a gradual increase in the adenosine deaminase transcript level, which may indicate a compensatory process in heart tissue to reduce the adenosine level after the tissue is in the wound-healing stage.
In addition, the reported differing responses to stress leading to acute heart injury in different inbred strains of mice may imply that in humans the inter-individual variations of susceptibility to stress/PTSD effects may have a genetic as well as an environmental component.
According to the authors the finding of acute heart injury in this PTSD animal model suggests common stress-induced heart impairment. These results may also suggest that further studies investigating the effects of acute/chronic stress or PTSD on heart tissue damage are warranted.
Source: Proc Natl Acad Sci U S A, 2014, 111:3188-93. doi: 10.1073/pnas.1400113111. Epub 2014 Feb 10.
Read more: pnas.org