Ghadrdoost Behshid, Aboutaleb Nahid, Nikougoftar Zarif Mahin, Nakhlestani Mojdeh, Haghjoo Majid, Sameie Shahram
Physiology Department, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
Cardiac Electrophysiology Research Center, Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran.
Iran J Basic Med Sci. 2019 Oct;22(10):1125-1131. doi: 10.22038/ijbms.2019.36362.8662.
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.
The study population was comprised 25 patients with PIC and 25 patients with normal left ventricular ejection fraction despite frequent PVCs. TNF-α, IL-6, IL10, and IFN-γ 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.
The flow cytometry findings showed that the median fluorescence intensity (MFI) of antibodies reacted with the IL-6 and TNF-α were higher in PIC group than the control group (-value<0.001). In ELISA, the levels of IL-6 (-value<0.001) and TNF-α (-value <0.001) and in RT-PCR the relative expression levels of IL-6 (-value<0.001) and TNF-α (-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 (-value>0.05).
In our patients with PIC, there was an elevation in the expression levels of IL-6 and TNF-α in PBMCs. This finding may provide further insights into the inflammatory pathways involved in PIC.
在理解室性早搏（PVC）诱发的心肌病（PIC）发病机制方面的最新进展表明炎症起关键作用。本研究旨在评估信使核糖核酸（mRNA）的表达以及白细胞介素-6（IL-6）、白细胞介素-10（IL-10）、肿瘤坏死因子α（TNF-α）和干扰素-γ（IFN-γ）的蛋白生成情况，以及两种与炎症和心血管疾病相关的循环微小核糖核酸（miRNA）；即miR-155和miR-146。
研究人群包括25例PIC患者和25例尽管频发PVC但左心室射血分数正常的患者。通过流式细胞术评估外周血单核细胞（PBMC）中TNF-α、IL-6、IL-10和IFN-γ水平，并通过实时聚合酶链反应评估其mRNA。我们通过酶联免疫吸附测定（ELISA）分析这些细胞因子的循环水平。还研究了两种循环微小核糖核酸，即miR-155和miR-146a。
流式细胞术结果显示，与IL-6和TNF-α反应的抗体的中位荧光强度（MFI）在PIC组高于对照组（P值<0.001）。在ELISA中，IL-6（P值<0.001）和TNF-α（P值<0.001）水平，以及在逆转录聚合酶链反应（RT-PCR）中IL-6（P值<0.001）和TNF-α（P值<0.001）的相对表达水平在PIC组显著更高。两组之间miR-155和miR-146a的相对表达水平无显著差异（P值>0.05）。
在我们的PIC患者中，PBMC中IL-6和TNF-α的表达水平升高。这一发现可能为深入了解PIC中涉及的炎症途径提供进一步线索。
