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, Levels of miR-574-5p were higher in patients with poor neurological outcome independently from targeted temperature management regimen, in both males (Supplementary Fig. 6A-C) and females (Supplementary Fig. 7A-C). Levels of miR-574-5p were higher in patients treated at 33°C compared to patients treated at 36°C, both males (Supplementary Fig. 6D) and females
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3A) and women ,
After adjustment with demographic and clinical variables, miR-574-5p remained an independent predictor of neurological outcome in females ,
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analysis revealed an association between miR-574-5p and survival at the end of the trial in both males and females ,
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,
, Le diagnostic et la prédiction de l'évolution des MCV reposent actuellement sur l'utilisation de biomarqueurs protéiques, mais doivent être améliorés pour optimiser la prise en charge des patients. Le transcriptome sanguin comprend l'ensemble des molécules ARN circulantes, qui sont présentes dans les cellules sanguines et libres dans le sang. Parmi elles, les ARN messagers (ARNm) codent pour des protéines alors que de petits ARN non codants, les microARNs (miARNs), Les maladies cardiovasculaires (MCV) représentent la première cause de mortalité dans le Monde et en Europe
, Nous avons émis l'hypothèse que le transcriptome sanguin, et en particulier les ARNm et les miARNs, avaient un potentiel de biomarqueur
, Dans une troisième étude, nous avons montré que les niveaux circulants de miR-574-5p étaient capables de discriminer les patients porteurs d'un AAT des personnes saines. De plus, le miR-574-5p est encapsulé dans des vésicules extracellulaires dans le sang, suggérant un rôle paracrine. Au cours des quatrième et cinquième études, nous avons montré que les niveaux circulants de miR-122-5p étaient des prédicteurs indépendants de l'évolution neurologique et de la survie à moyen terme post-AC, et capable d'améliorer les modèles de prédiction existants, nous avons montré que l'héparine endogène pouvait induire une inhibition de la transcription inverse couplée à la PCR quantitative lors de la mesure des miARNs circulants et que ce paramètre devait être pris en compte lors de l'étude du transcriptome sanguin
, En conclusion, ce travail de thèse a permis la découverte ou la confirmation de la valeur de biomarqueurs potentiels de transcrits et miARNs dans différentes MCV. Cependant, leur capacité de biomarqueur devra être validée dans d'autres études à grande échelle et à l'aide d'autres techniques avant d'envisager leur utilisation en clinique
Mots clés : maladies cardiovasculaires, biomarqueurs diagnostiques, biomarqueurs prédictifs, transcriptome sanguin, microARN ,
, Diagnosis and prediction of outcome of CVD currently rely on the use of protein biomarkers, but should be improved to optimize patient healthcare. Blood transcriptome contains all RNA molecules present in blood cells and in the acellular compartment. Among them, messenger RNA (mRNA) code for proteins whereas small non coding RNA, microRNA (miRNA), Cardiovascular disease (CVD) is the main cause of mortality in the World and in Europe
, We hypothesized that blood transcriptome, mRNA and miRNA in particular, had a potential as biomarker, diagnostic or prognostic
, inhibition of reverse transcription and quantitative PCR reaction used to measure miRNAs expressed in the blood, and that this parameter should be considered for studies on blood transcriptome. Secondly, we showed that 3 transcripts (coding for genes LMNB1, LTBP4, TGFBR1) expressed in whole blood, were independent predictors of cardiac function alteration at 4 months post-MI. Furthermore, the inclusion of these 3 transcripts in a prediction model containing clinical variables had an incremental predictive value. In a third study, we showed that circulating levels of miR-574-5p were able to discriminate patients with TAA from healthy controls. Furthermore, miR-574-5p was encapsulated in extracellular vesicles in the blood, suggesting a paracrine role. In the fourth and fifth studies, we showed that circulating levels of miR-122-5p were independent predictors of neurological outcome and survival at middle term post-CA