According to a team of researchers from the Medical University of Vienna, Austria, a variety of organ systems, including liver and spleen, are involved in the co-ordination of the organism’s response to a heart attack, a medical emergency in which the supply of blood to the heart is suddenly and severely reduced or cut off.
A variety of organ systems are involved in the coordination of the organism’s response to myocardial infarction by the production and release of paracrine factors; for initiation of this paracrine feedback loops a variety of transcription factors are regulated in different organs. Image credit: Zimmermann et al, doi: 10.18632/oncotarget.17955.
“We demonstrated the need to rethink our tunnel vision that focuses solely on the heart in the event of a heart attack (myocardial infarction),” said Matthias Zimmermann, a PhD student at the Medical University of Vienna and first author of the paper reporting the results in the journal Oncotarget.
“For the first time we were able to scientifically describe the full picture of a myocardial infarction. This contributes enormously to our understanding in terms of systems biology.”
Zimmermann and co-authors investigated the systemic responses in an animal model of myocardial infarction. They were able to show that multiple genes are involved the condition.
“Myocardial infarction changed the expression of 8,903 genes in myocardial-, 856 in hepatic- and 338 in splenic tissue,” they said.
“Identification of myocardial region specific differences as well as expression profiling of distant organs revealed clear gene-regulation patterns within the first 24 hours after ischemia.”
At the same time, the researchers were able to ascribe a major role to Kruppel like factor 4 (Klf4), a protein that is important for activating many other genes.
“Transcription factor binding site analysis of up- and downregulated genes in hepatic and splenic tissue revealed two major points: the enrichment pattern was comparable in both tissues-types; and some of the identified transcription factors, including Klf4, seem to play a role in myocardial infarction adaptational processes not only in the heart but also in other organs, such as liver and spleen,” the authors said.
“Our data emphasize that Klf4 is involved in cell differentiation, cell growth and cell cycle in multiple tissues.”
“In the context of an inflammatory response after acute myocardial infarction and consistent with previous reports, Klf4 may be a critical regulator in the transcriptional network controlling lymphocyte differentiation.”
They added: “although the animal model we used is closely related to human ischemic heart disease, more sophisticated experiments are needed to validate the pathways identified and their contribution to disease in the human system.”
“The new findings do not call into question the current acute treatment for heart attacks but they do open up the debate as to whether future treatment should be viewed systemically and should address different areas of the body.”
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Matthias Zimmermann et al. Analysis of region specific gene expression patterns in the heart and systemic responses after experimental myocardial ischemia. Oncotarget, published online May 17, 2017; doi: 10.18632/oncotarget.17955
