MiR423-5p As a Circulating Biomarker for Heart Failure

Abstract

Rationale: Aberrant expression profiles of circulating microRNAs (miRNAs) have been described in various diseases and provide high sensitivity and specificity. We explored circulating miRNAs as potential biomarkers in patients with heart failure (HF). Objective: The goal of this study was to determine whether miRNAs allow to distinguish clinical HF not only from healthy controls but also from non-HF forms of dyspnea. Methods and Results: A miRNA array was performed on plasma of 12 healthy controls and 12 HF patients. From this array, we selected 16 miRNAs for a second clinical study in 39 healthy controls and in 50 cases with reports of dyspnea, of whom 30 were diagnosed with HF and 20 were diagnosed with dyspnea attributable to non-HF-related causes. This revealed that miR423-5p was specifically enriched in blood of HF cases and receiver-operator-characteristics (ROC) curve analysis showed miR423-5p to be a diagnostic predictor of HF, with an area under the curve of 0.91 (P<0.001). Five other miRNAs were elevated in HF cases but also slightly increased in non-HF dyspnea cases. Conclusion: We identify 6 miRNAs that are elevated in patients with HF, among which miR423-5p is most strongly related to the clinical diagnosis of HF. Recent studies have unveiled powerful and unexpected roles for microRNAs (miRNAs) in cardiovascular diseases, including HF. There are estimated to be more than 1000 different miRNAs, many of which are expressed in a tissue and cell-specific manner. 3 It was discovered only recently that miRNAs are also abundantly present in blood, where they can be detected in plasma, platelets, and erythrocytes, as well as in nucleated blood cells. 4 Aberrant expression profiles of miRNAs have been identified in blood of subjects with sickle cell anemia, prostate cancer, lung cancer and myocardial injury. 4 -6 This led us to hypothesize that miRNA profiling can also be used for diagnostic approaches in HF.Here we explored whether circulating miRNAs can be used as biomarkers in patients with HF. We first performed miRNA arrays on RNA isolated from plasma and selected 16 miRNAs expressed differentially in HF patients. Next, we evaluated these miRNAs in a second group of patients, consisting of 50 cases with reports of dyspnea, of whom 30 were diagnosed with HF (HF cases) and 20 were diagnosed to have dyspnea attributable to non-HF causes (non-HF cases). One circulating miRNA in particular, miR423-5p, was able to distinguish HF cases from non-HF cases.In conclusion, we demonstrate a number of miRNAs as putative biomarkers for HF, in particular miR423-5p. MethodsHuman plasma samples were obtained with informed consent under a general waiver by the Academic Medical Center institutional review board for the proper secondary use of human material. For the dyspnea registry, plasma samples were obtained as part of a multicenter effort involving 3 centers in The Netherlands. Experiments described were performed on samples obtained at the Academic Medical Center. For a detailed description of the dyspnea registry,...

Comparative RNA-sequencing analysis of myocardial and circulating small RNAs in human heart failure and their utility as biomarkers

“…Increases in circulating miRNAs upon cell damage have been detected by RT-PCR-based approaches for liver, brain, and skeletal muscle (5), as well as heart (19,46 instances miRNAs even performed better than established protein biomarkers (5). Our analysis indicated that heart-specific myomirs performed similar to the highly sensitive cTnI assay, but we were unable to verify the utility of any recently proposed miRNA biomarker for HF (18,(20)(21)(22). Considering that sRNAseq experiments capture a wide spectrum of miRNAs as well as fragments of other classes of RNAs, and can be performed with low ng quantities of total RNA recoverable from 250 μL plasma or serum, this approach holds great potential for future RNA biomarker discovery.…”

“…S1) were shown to contribute to muscle or myocardial function (8, 9). miRNAs and other classes of RNA have been profiled in failing human myocardium (10)(11)(12)(13)(14)(15)(16)(17), and a selected subset was also investigated as circulating biomarkers in HF (18)(19)(20)(21)(22)(23)(24). However, in these studies heart tissue and circulating miRNA abundance changes were not acquired simultaneously to correlate changes in tissue versus circulating miRNA composition.…”

MicroRNAs: um novo paradigma no tratamento e diagnóstico da insuficiência cardíaca?

“…However, the need for an invasive procedure to obtain samples from the myocardium makes the clinical application of this approach very limited. However, recent evidence has shown that the c-miRNA miR-423-5p shows an increased expression during heart failure and can be used as a biomarker 37 .…”

Exercício físico e microRNAs: novas fronteiras na insuficiência cardíaca

“…In order to determine which could be used as biomarkers in HF, Tijsen et al 40 compared the expression profile of miRNAs in the plasma of 12 healthy subjects with 12 patients admitted for acute HF. Among 108 miRNAs that showed significant difference between the groups, 16 were selected and validated in a larger group, including 30 patients with HF, 20 who had dyspnea due to other causes rather than the HF, and a third group of 39 healthy individuals.…”