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Association between cytokines and two circulating micro-RNAs and development of premature ventricular contractions-induced cardiomyopathy.

ABSTRACT: Objectives:Recent progress in understanding the pathogenesis of premature ventricular contraction (PVC)-induced cardiomyopathy (PIC) has suggested a key role for inflammation. The aim of this study was to evaluate the expression of messenger RNAs (mRNAs) and the protein production of interleukin-6 (IL-6), IL-10, tumor necrosis factor alpha (TNF-?) and interferon-? (IFN-?) and two circulating micro-RNAs related to inflammation and cardiovascular disease; miR-155 and miR-146. Materials and Methods:The study population was comprised 25 patients with PIC and 25 patients with normal left ventricular ejection fraction despite frequent PVCs. TNF-?, IL-6, IL10, and IFN-? levels were evaluated in peripheral blood mononuclear cells (PBMCs) by flow cytometry and their mRNAs were assessed by real time PCR. We analyzed circulating levels of these cytokines by enzyme linked immunosorbent assay (ELISA). Two circulating micro-RNAs, miR-155 and miR-146a, were also investigated. Results:The flow cytometry findings showed that the median fluorescence intensity (MFI) of antibodies reacted with the IL-6 and TNF-? were higher in PIC group than the control group (P-value<0.001). In ELISA, the levels of IL-6 (P-value<0.001) and TNF-? (P-value <0.001) and in RT-PCR the relative expression levels of IL-6 (P-value<0.001) and TNF-? (P-value<0.001) were significantly higher in the PIC group. The relative expression levels of miR-155 and miR-146a were not significantly different between 2 groups (P-value>0.05). Conclusion:In our patients with PIC, there was an elevation in the expression levels of IL-6 and TNF-? in PBMCs. This finding may provide further insights into the inflammatory pathways involved in PIC.

SUBMITTER: Ghadrdoost B

PROVIDER: S-EPMC6885395 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Association between cytokines and two circulating micro-RNAs and development of premature ventricular contractions-induced cardiomyopathy.

Ghadrdoost Behshid B Aboutaleb Nahid N Nikougoftar Zarif Mahin M Nakhlestani Mojdeh M Haghjoo Majid M Sameie Shahram S

Iranian journal of basic medical sciences 20191001 10

<h4>Objectives</h4>Recent progress in understanding the pathogenesis of premature ventricular contraction (PVC)-induced cardiomyopathy (PIC) has suggested a key role for inflammation. The aim of this study was to evaluate the expression of messenger RNAs (mRNAs) and the protein production of interleukin-6 (IL-6), IL-10, tumor necrosis factor alpha (TNF-α) and interferon-γ (IFN-γ) and two circulating micro-RNAs related to inflammation and cardiovascular disease; miR-155 and miR-146.<h4>Materials ...[more]

PMID: 31998452

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Project description:Mechanisms behind development of premature ventricular contraction (PVC)-induced cardiomyopathy remain unclear. PVCs may adversely modulate the autonomic nervous system to promote development of heart failure. Afferent neurons in the inferior vagal (nodose) ganglia transduce cardiac activity and modulate parasympathetic output. Effects of PVCs on cardiac parasympathetic efferent and vagal afferent neurotransmission are unknown. The purpose of this study was to evaluate effects of PVCs on vagal afferent neurotransmission and compare these effects with a known powerful autonomic modulator, myocardial ischemia. In 16 pigs, effects of variably coupled PVCs on heart rate variability (HRV) and vagal afferent neurotransmission were evaluated. Direct nodose neuronal recordings were obtained in vivo, and cardiac-related afferent neurons were identified based on their response to cardiovascular interventions, including ventricular chemical and mechanical stimuli, left anterior descending (LAD) coronary artery occlusion, and variably coupled PVCs. On HRV analysis before versus after PVCs, parasympathetic tone decreased (normalized high frequency: 83.6?±?2.8 to 72.5?±?5.3; P < 0.05). PVCs had a powerful impact on activity of cardiac-related afferent neurons, altering activity of 51% of neurons versus 31% for LAD occlusion (P < 0.05 vs. LAD occlusion and all other cardiac interventions). Both chemosensitive and mechanosensitive neurons were activated by PVCs, and their activity remained elevated even after cessation of PVCs. Cardiac afferent neural responses to PVCs were greater than any other intervention, including ischemia of similar duration. These data suggest that even brief periods of PVCs powerfully modulate vagal afferent neurotransmission, reflexly decreasing parasympathetic efferent tone.NEW & NOTEWORTHY Premature ventricular contractions (PVCs) are common in many patients and, at an increased burden, are known to cause heart failure. This study determined that PVCs powerfully modulate cardiac vagal afferent neurotransmission (exerting even greater effects than ventricular ischemia) and reduce parasympathetic efferent outflow to the heart. PVCs activated both mechano- and chemosensory neurons in the nodose ganglia. These peripheral neurons demonstrated adaptation in response to PVCs. This study provides additional data on the potential role of the autonomic nervous system in PVC-induced cardiomyopathy.

Dataset Information

Association between cytokines and two circulating micro-RNAs and development of premature ventricular contractions-induced cardiomyopathy.

Publications

Association between cytokines and two circulating micro-RNAs and development of premature ventricular contractions-induced cardiomyopathy.

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