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Transcriptomic profiling of the four adenosine receptors in human leukocytes of heart failure patients.

ABSTRACT: In this study the transcriptomic profiling of adenosine receptors (ARs) in human leukocytes of heart failure (HF) patients as a function of clinical severity, assessing the possible changes with respect to healthy subjects (C), was evaluated. Total RNA was extracted from leukocytes of C (n = 8) and of HF patients (NYHA I-II n = 9; NYHA III-IV n = 14) with a PAXgene Blood RNA Kit. An increase as a function of clinical severity was observed in each AR (A1R: C = 0.02 ± 0.009, NYHA I-II = 0.21 ± 0.09, NYHA III-IV = 3.6 ± 1.3, P = 0.03 C versus NYHA III-IV, P = 0.02 NYHA I-II versus NYHA III-IV; A2aR: C = 0.2 ± 0.05, NYHA I-II = 0.19 ± 0.04, NYHA III-IV = 1.32 ± 0.33, P = 0.005 C versus NYHA III-IV, P = 0.003 NYHA I-II versus NYHA III-IV; A2bR: C = 1.78 ± 0.36, NYHA I-II = 1.35 ± 0.29, NYHA III-IV = 4.07 ± 1.21, P = 0.03: NYHA I-II versus NYHA III-IV; A3R: C = 0.76 ± 0.21, NYHA I-II = 0.94 ± 0.19, NYHA III-IV = 3.14 ± 0.77, P = 0.01 C versus NYHA III-IV and NYHA I-II versus NYHA III-IV, resp.). The mRNA expression of the ectonucleoside triphosphate diphosphohydrolase (CD39) and the ecto-5'-nucleotidase (CD73) were also evaluated. They resulted up-regulated. These findings show that components of adenosine metabolism and signalling are altered to promote adenosine production and signalling in HF patients. Thus, HF may benefit from adenosine-based drug therapy after confirmation by clinical trials.

SUBMITTER: Cabiati M

PROVIDER: S-EPMC3722840 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Transcriptomic profiling of the four adenosine receptors in human leukocytes of heart failure patients.

Cabiati Manuela M Caruso Raffaele R Verde Alessandro A Sabatino Laura L Morales Maria-Aurora MA Del Ry Silvia S

BioMed research international 20130708

In this study the transcriptomic profiling of adenosine receptors (ARs) in human leukocytes of heart failure (HF) patients as a function of clinical severity, assessing the possible changes with respect to healthy subjects (C), was evaluated. Total RNA was extracted from leukocytes of C (n = 8) and of HF patients (NYHA I-II n = 9; NYHA III-IV n = 14) with a PAXgene Blood RNA Kit. An increase as a function of clinical severity was observed in each AR (A1R: C = 0.02 ± 0.009, NYHA I-II = 0.21 ± 0.0 ...[more]

PMID: 23936818

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Project description:AimsMulticellular organisms maintain vital functions through intercellular communication. Release of extracellular vesicles that carry signals to even distant target organs is one way of accomplishing this communication. MicroRNAs can also be secreted from the cells in exosomes and act as paracrine signalling molecules. In addition, microRNAs have been implicated in the pathogenesis of a large number of diseases, including cardiovascular diseases, and are considered as promising candidate biomarkers due to their relative stability and easy quantification from clinical samples. Pericardial fluid contains hormones secreted by the heart and is known to reflect the cardiac function. In this study, we sought to investigate whether pericardial fluid contains microRNAs and if so, whether they could be used to distinguish between different cardiovascular pathologies and disease stages.Methods and resultsPericardial fluid was collected from heart failure patients during open-heart surgery. MicroRNA profiles of altogether 51 patients were measured by quantitative real-time PCR (qPCR) using Exiqon human panels I and II. On the average, 256 microRNAs were detected per sample, and 70 microRNAs out of 742 profiled microRNAs were detected in every sample. The five most abundant microRNAs in pericardial fluid were miR-21-5p, miR-451a, miR-125b-5p, let-7b-5p and miR-16-5p. No specific signatures for cardiovascular pathologies or clinically assessed heart failure stages could be detected from the profiles and, overall, microRNA profiles of the samples were found to be very similar despite the heterogeneity in the study population.ConclusionMeasured microRNA profiles did not separate the samples according to the clinical features of the patients. However, several previously identified heart failure marker microRNAs were detected. The pericardial fluid microRNA profile appeared to be a result of an active and selective secretory process indicating that microRNAs may act as paracrine signalling factors by mediating the local crosstalk between cardiac cells.

Project description:Venom based research is exploited to find novel candidates for the development of innovative pharmacological tools, drug candidates and new ingredients for cosmetic and agrochemical industries. Moreover, venomics, as a well-established approach in systems biology, helps to elucidate the genetic mechanisms of the production of such a great molecular biodiversity. Today the advances made in the proteomics, transcriptomics and bioinformatics fields, favor venomics, allowing the in depth study of complex matrices and the elucidation even of minor compounds present in minute biological samples. The present study illustrates a rapid and efficient method developed for the elucidation of venom composition based on NextGen mRNA sequencing of venom glands and LC-MS/MS venom proteome profiling. The analysis of the comprehensive data obtained was focused on cysteine rich peptide toxins from four spider species originating from phylogenetically distant families for comparison purposes. The studied species were Heteropoda davidbowie (Sparassidae), Poecilotheria formosa (Theraphosidae), Viridasius fasciatus (Viridasiidae) and Latrodectus mactans (Theridiidae). This led to a high resolution profiling of 284 characterized cysteine rich peptides, 111 of which belong to the Inhibitor Cysteine Knot (ICK) structural motif. The analysis of H. davidbowie venom revealed a high richness in term of venom diversity: 95 peptide sequences were identified; out of these, 32 peptides presented the ICK structural motif and could be classified in six distinct families. The profiling of P. formosa venom highlighted the presence of 126 peptide sequences, with 52 ICK toxins belonging to three structural distinct families. V. fasciatus venom was shown to contain 49 peptide sequences, out of which 22 presented the ICK structural motif and were attributed to five families. The venom of L. mactans, until now studied for its large neurotoxins (Latrotoxins), revealed the presence of 14 cysteine rich peptides, out of which five were ICK toxins belonging to the CSTX superfamily. This in depth profiling of distinct ICK peptide families identified across the four spider species highlighted the high conservation of these neurotoxins among spider families.

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Dataset Information

Transcriptomic profiling of the four adenosine receptors in human leukocytes of heart failure patients.

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Transcriptomic profiling of the four adenosine receptors in human leukocytes of heart failure patients.

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