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Parkinson’s disease (PD) is a complex and heterogeneous disorder involving multiple genetic and environmental influences. Although a wide range of PD risk factors and clinical markers for the symptomatic motor stage of the disease have been identified, there are still no reliable biomarkers available for the early pre-motor phase of PD and for predicting disease progression. High-throughput RNA-based biomarker profiling and modeling may provide a means to exploit the joint information content from a multitude of markers to derive diagnostic and prognostic signatures. In the field of PD biomarker research, currently, no clinically validated RNA-based biomarker models are available, but previous studies reported several significantly disease-associated changes in RNA abundances and activities in multiple human tissues and body fluids. Here, we review the current knowledge of the regulation and function of non-coding RNAs in PD, focusing on microRNAs, long non-coding RNAs, and circular RNAs. Since there is growing evidence for functional interactions between the heart and the brain, we discuss the benefits of studying the role of non-coding RNAs in organ interactions when deciphering the complex regulatory networks involved in PD progression. We finally review important concepts of harmonization and curation of high throughput datasets, and we discuss the potential of systems biomedicine to derive and evaluate RNA biomarker signatures from high-throughput expression data.

Outcome prognostication after cardiac arrest (CA) is challenging. Current multimodal prediction approaches would benefit from new biomarkers. MicroRNAs constitute a novel class of disease markers and circulating levels of brain-enriched ones have been associated with outcome after CA. To determine whether these levels reflect the extent of brain damage in CA patients, we assessed their correlation with neuron-specific enolase (NSE), a marker of brain damage. Blood samples taken 48 h after return of spontaneous circulation from two groups of patients from the Targeted Temperature Management trial were used. Patients were grouped depending on their neurological outcome at six months. Circulating levels of microRNAs were assessed by sequencing. NSE was measured at the same time-point. Among the 673 microRNAs detected, brain-enriched miR9-3p, miR124-3p and miR129-5p positively correlated with NSE levels (all p < 0.001). Interestingly, these correlations were absent when only the good outcome group was analyzed (p > 0.5). Moreover, these correlations were unaffected by demographic and clinical characteristics. All three microRNAs predicted neurological outcome at 6 months. Circulating levels of brain-enriched microRNAs are correlated with NSE levels and hence can reflect the extent of brain injury in patients after CA. This observation strengthens the potential of brain-enriched microRNAs to aid in outcome prognostication after CA.

Rationale. The value of microRNAs (miRNAs) as biomarkers has been addressed in various clinical contexts. Initial studies suggested that miRNAs, such as the brain-enriched miR-124-3p, might improve outcome prediction after out-of-hospital cardiac arrest. The aim of this study is to determine the prognostic value of miR-122-5p in a large cohort of comatose survivors of out-of-hospital cardiac arrest. Methods. We analyzed 590 patients from the Targeted Temperature Management trial (TTM-trial). Circulating levels of miR-122-5p were measured in serum samples obtained 48 hours after return of spontaneous circulation. The primary end-point was poor neurological outcome at 6 months evaluated by the cerebral performance category score. The secondary end-point was survival at the end of the trial. Results. Forty-eight percent of patients had a poor neurological outcome at 6 months and 43% were dead at the end of the trial. Levels of miR-122-5p were lower in patients with poor neurological outcome compared to patients with good neurological outcome (p<0.001), independently of targeted temperature management regimen. Levels of miR-122-5p were significant univariate predictors of neurological outcome (odds ratios (OR), 95% confidence intervals (CI): 0.71 [0.57-0.88]). In multivariable analyses, miR-122-5p was an independent predictor of neurological outcome and improved the predictive value of a clinical model including miR-124-3p (integrated discrimination improvement of 0.03 [0.02-0.04]). In Cox proportional hazards models, miR-122-5p was a significant predictor of survival at the end of the trial. Conclusion. Circulating levels of miR-122-5p improve the prediction of outcome after out-of-hospital cardiac arrest.

La cardiopatía isquémica es la enfermedad que causa mayor número de muertes e incapacidad en los países desarrollados. El incremento del tejido adiposo en la obesidad, en particular el componente visceral, constituye un importante factor de riesgo cardiovascular. El tejido adiposo epicárdico (TAE) se distribuye de forma preferente siguiendo la adventicia de las arterias coronarias, pudiendo ejercer un efecto paracrino sobre las mismas y/o el miocardio subyacente. Debido a las diferencias que existen entre los tejidos adiposos según su ubicación y a la interacción entre el tejido adiposo con otros tejidos (ya sea de manera paracrina o endocrina), se han planteado los siguientes objetivos: o Analizar las diferencias de expresión proteica existentes entre TAE y tejido adiposo subcutáneo (TAS) de pacientes sometidos a cirugía cardíaca. o Comparar la secreción del tejido adiposo dependiendo de su localización. o Determinar los niveles de expresión y secreción proteica en pacientes afectados por cardiopatía isquémica frente a pacientes sin coronariopatía. En el desarrollo de esta tesis, se ha demostrado que el TAE presenta mayor estrés oxidativo que el TAS en pacientes sometidos a cirugía cardíaca. La expresión de enzimas anti-oxidantes que presentan diferencias en cuanto a su cantidad o a modificaciones postraduccionales (CATA, GSTP1, PDIA1 y PGAM1) sugiere una posible relación de ellos con el mayor estrés oxidativo encontrado en este tejido. Gracias a la separación de los componentes celulares del tejido adiposo, se ha podido evidenciar que los cambios en la producción de radicales libres entre los dos tejidos provienen de la fracción adipocitaria. Las diferencias entre estos dos tejidos no se limitaban sólo a esta observación, sino que también se han encontrado cambios a nivel de la secreción. Así, el TAE es más activo, en términos de secreción proteica, que el TAS. En este aspecto, el TAE secreta al medio de cultivo mayor cantidad de moléculas de transporte lipídico (