Abstract

Heart failure (HF) is the typical terminal stage of cardiac diseases involving inflammatory states. The function of microRNAs (miRNAs) in the progress of HF remains poorly understood. In this study, real-time PCR results showed a decreased expression of miRNA-181b (miR-181b) in HF patients compared with healthy individuals. Besides, miR-181b expressions were negatively correlated with hypersensitive C-reactive protein (hsCRP) levels in the serum of HF patients. Receiver operator characteristic (ROC) curve analysis showed that miR-181b was a diagnostic predictor of HF, and the area under the curve was 0.970 (DCM-induced HF group) and 0.962 (ICM-induced HF group). Strikingly, in HF rats induced by isoproterenol (ISO), the expression of miR-181b of heart tissue was suppressed before tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) increase, as revealed by western blot and real-time PCR. Besides, the overexpression of miR-181b also decreased the expression of TNF-α, IL-1β, and IL-6 in lipopolysaccharide- (LPS-) induced neonatal cardiomyocytes. In conclusion, our results revealed that miR-181b might be a potential biomarker for HF and provided a novel target for anti-inflammatory therapy.

Highlights

  • Heart failure (HF), as the typical terminal stage of cardiovascular diseases, has high morbidity and mortality worldwide

  • Myocardium ischemia and dilated cardiomyopathy are two important pathological processes leading to the progressing of HF, and both of which are involved in inflammatory mechanisms [1]

  • Our study found that the expression of miR-181b in the serum of HF patients was down-regulated, and it was negatively correlated with the level of hypersensitive C-reactive protein (hsCRP)

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Summary

Introduction

Heart failure (HF), as the typical terminal stage of cardiovascular diseases, has high morbidity and mortality worldwide. Myocardium ischemia and dilated cardiomyopathy are two important pathological processes leading to the progressing of HF, and both of which are involved in inflammatory mechanisms [1]. In HF, proinflammatory cytokines such as IL-6 and TNF-α are considered to contribute to disease progression by exerting on the heart and circulation [2]. Several studies have shown that HF patients are characterized by sustained immune activation and elevated levels of circulating proinflammatory cytokines, such as TNF-α, IL-6, and IL-1β [3]. Biomarkers play an important role in the clinical management and risk stratification for cardiovascular diseases (CVD) and HF [5]. Recent trends indicate that the measurement of diagnostic biomarkers in novel biological specimens (such as the saliva) is becoming increasingly popular due to its noninvasive nature [7,8,9]. Protein assays are the most widely used, followed by Disease Markers cellular and molecular assays; the clinical application of microRNA analysis has recently received a lot of attention [6]

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