Abstract 19167: Transcriptome Remodeling of Cardiac Autonomic Nervous System Following Myocardial Infarction In Porcine
Background: Cardiac autonomic nervous system (ANS), including spinal cord (SC), stellate ganglia (SG) and dorsal root ganglia (DRG), plays a critical role in cardiac regulation of contractile function and rhythm. Abnormal function of ANS following myocardial infarct has been implicated as an important contributor and a novel therapeutic target for arrhythmia following cardiac injury. However, the underlying mechanism for the pathological changes in ANS following cardiac injury remains to be established.
Methods and Results: In this study, we performed transcriptome analysis of ANS tissues in Yorkshire pigs following either acute (3 to 5 hours) or chronic (8 weeks) myocardial infarction. Using deep RNA-Seq, we compared the gene expression profiles in the T1-T4 stellate ganglia, dorsal root ganglia and dorsal horn of spinal cord obtained from the untreated, acute and chronic infarcted animals. Based on Principal Component Analysis and unsupervised clustering, we identified specific transcriptome changes in the ANS tissues associated with myocardial infarction. Based on Ingenuity Pathway Analysis, we found cell death signaling together with p53 mediated pathway were among the genes most affected in the chronic infarct SG and DRG. TUNEL staining confirmed a significant induction of apoptotic signal in both SG and DRG in the chronic post-infarct animals but not in the control or the acute-infarct groups. In contrast, the most affected genes in the dorsal horn following MI implicate cellular repair, GABA signaling and extracellular matrix remodeling. Importantly, these molecular changes were observed specifically in the post-MI thoracic tissues but not in their counterparts obtained from lumbar sections.
Conclusion: Transcriptome analysis revealed a profound impact of myocardial injury on the gene expression in the innervating ANS. Loss of neuron cell viability in SG and DRG, and pathological remodeling in SC are potential novel mechanisms leading to abnormal ANS function, cardiac arrhythmia and dysfunction.
Author Disclosures: C. Gao: None. K. Howard-Quijano: None. T. Takamiya: None. W. Zhou: None. C.D. Rau: None. Y. Song: None. A. Mahajan: None. Y. Wang: None.
- © 2016 by American Heart Association, Inc.