Inflammatory and apoptotic remodeling in autonomic nervous system following myocardial infarction

Abstract

BackgroundChronic myocardial infarction (MI) triggers pathological remodeling in the heart and cardiac nervous system. Abnormal function of the autonomic nervous system (ANS), including stellate ganglia (SG) and dorsal root ganglia (DRG) contribute to increased sympathoexcitation, cardiac dysfunction and arrythmogenesis. ANS modulation is a therapeutic target for arrhythmia associated with cardiac injury. However, the molecular mechanism involved in the pathological remodeling in ANS following cardiac injury remains to be established.Methods and resultsIn this study, we performed transcriptome analysis by RNA-sequencing in thoracic SG and (T1-T4) DRG obtained from Yorkshire pigs following either acute (3 to 5 hours) or chronic (8 weeks) myocardial infarction. By differential expression and weighted gene co-expression network analysis (WGCNA), we identified significant transcriptome changes and specific gene modules in the ANS tissues in response to myocardial infarction at either acute or chronic phases. Both differential expressed genes and the member genes of the WGCNA gene module associated with post-infarct condition were significantly enriched for inflammatory signaling and apoptotic cell death. Targeted validation analysis supported a significant induction of inflammatory and apoptotic signal in both SG and DRG following myocardial infarction, along with cellular evidence of apoptosis induction based on TUNEL analysis. Importantly, these molecular changes were observed specifically in the thoracic segments but not in their counterparts obtained from lumbar sections.ConclusionMyocardial injury leads to time-dependent global changes in gene expression in the innervating ANS. Induction of inflammatory gene expression and loss of neuron cell viability in SG and DRG are potential novel mechanisms contributing to abnormal ANS function which can promote cardiac arrhythmia and pathological remodeling in myocardium.

Humanin analog enhances the protective effect of dexrazoxane against doxorubicin-induced cardiotoxicity

“…Quantification of cardiomyocyte apoptosis by colocalization of tropomyosin and DNA fragmentation. Formalin-fixed and paraffinembedded transverse ventricular heart sections from each mouse were used to colocalize expression of tropomyosin, a myocardium marker, and TUNEL for the detection of apoptosis (13,31). Briefly, after deparaffinization and rehydration, heart sections received antigen retrieval in citrate buffer (pH 6.0) with boiling for 30 min.…”

Aging-Induced Biological Changes and Cardiovascular Diseases

“…According to Wang et al (2010) [ 179 ], cardiac remodeling which is an adaptive process often leads to electrical instability, ventricular arrhythmia, cardiac dysfunction, and the death of cardiomyocytes. The incidence of cardiac dysfunction, arrhythmogenesis, and myocardial infarction has been linked to an increase of sympathetic excitation during the remodeling of ANS function as seen in the starred ganglia and dorsal root ganglia [ 180 ]. The ganglionic compromise of the autonomic plexuses during adolescence increases susceptibility to atrial fibrillation, micro- and macrostructural changes in the atrial myocardium, intracellular damage (myocyte degeneration, apoptosis), and extracellular fibrotic proliferation [ 181 ].…”

Baicalin Depresses the Sympathoexcitatory Reflex Induced by Myocardial Ischemia via the Dorsal Root Ganglia

“…Using horseradish peroxidase (HRP), our previous works tested by retrograde tracing showed that the cervical and upper thoracic dorsal root ganglia were related to the signaling transmission induced by MI ( Liu et al, 2013 ; Tu et al, 2013 ). It was reported that changes in gene expression localized to thoracic spinal cord only, with no change in gene expression in lumber DRG after MI or infarction and the expression of immune modulators and apootic genes were observed in the thoracic DRG but not in the lumbar DRG following MI ( Gao et al, 2017 ). Our results showed that the expression changes of P2Y 12 mRNA and protein localized to cervical and upper thoracic spinal cord DRGs only and no changes were observed for the expression of P2Y 12 mRNA and protein in lumbar DRGs from the same post-MI animals.…”