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|Autori: ||Martinez Lopez de Arroyabe, Blanca|
|Supervisore afferente all'Università: ||LIVI, UGOLINO|
|Titolo: ||Plasmatic microRNAs in advanced heart failure patients supported by left ventricular assist devices (LVAD)|
|Abstract (in inglese): ||Nowadays, heart failure remains a global problem responsible of a high mortality. Despite spectacular advances made in the past three decades in cardiovascular medicine and surgery, the prognosis of heart failure is worse than that of most cancers (1).
The gold standard therapy for refractory end-stage heart failure is currently heart transplantation. However, the increasing shortage of donors has led to the development of mechanical assist devices to support and improve the organ function of patients while on waiting for transplantation. The good results of ventricular assist devices “as a bridge to transplantation” has expanded the application of VAD to be implanted “as a bridge to decision”, “as a bridge to candidacy”, “as a bridge to recovery” and, increasingly, “as a destination therapy” (DT) (2). In 2001 the REMATCH (Randomized Evaluation of Mechanical Assistance for the Treatment OF Congestive Heart Failure) study first demonstrated that long-term support with a left ventricular assist device resulted in substantial improvement in survival in patients with severe heart failure who were not candidates for cardiac transplantation compared with any known optimal medical therapy addressed to optimize organ perfusion and minimize symptoms of congestive heart failure (3).
Several mechanisms have been advocated to contribute to pathophysiology of heart failure, including genetic mechanisms. In this
context, short non-coding RNAs called microRNA (miRNAs) block gene expression and protein translation. These molecules are crucial to calcium cycling and ventricular hypertrophy. The actions of miRNAs can be blocked by a new class of drugs, antagomirs, some of which have been shown to improve cardiac function in animal models. Moreover, the microRNAs have been proposed as biomarkers of heart failure or cardiac function recovery. For example, increased concentrations of miRNA34, 192 and 194 are predictive of development of heart failure in patients after acute myocardial infarction (4).
Matkovich and coworkers (5) reported that the miRNA-499 levels of patients with heart failure were greatly increased and almost completely normalized after they had been placed on left ventricular assist device. In selected patients, LVAD can lead to myocardial recovery and explantation of the device. Maybe circulating miRNA could be useful prognostic biomarkers of cardiac reverse remodeling in LVAD patients but further investigations are warranted to understand the real role of miRNAs in this setting and their potential utility. The aim of this study is to evaluate the modification of some miRNAs related to myocardial fibrosis, ventricular remodelling and platelet function in patients with heart failure compare with healthy volunteers and in heart failure patients after LVAD positioning at short and long term periods (6-10 day, 2-3 months, 12-18 months).
To analyze the modification of P-Selectin in patients supported by VAD and its correlation with thrombotic events.|
|Parole chiave: ||Advanced heart failure; Left ventricular assist devices; VAD; Plasmatic miRNAs|
|MIUR : ||Settore MED/23 - Chirurgia Cardiaca|
Settore MED/11 - Malattie Dell'Apparato Cardiovascolare
|Corso di dottorato: ||Dottorato di ricerca in Medicina cellulare e molecolare|
|Ciclo di dottorato: ||29|
|Università di conseguimento titolo: ||Università degli Studi di Udine|
|Luogo di discussione: ||Udine|
|Altre informazioni: ||Co-supervisore: Antonio Paolo Beltrami|
|Citazione: ||Martinez Lopez de Arroyabe, B. Plasmatic microRNAs in advanced heart failure patients supported by left ventricular assist devices (LVAD). (Doctoral Thesis, Università degli Studi di Udine, 2017).|
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