ARTRITIS REUMATOIDE Y ENFERMEDAD CARDIOVASCULAR. Papel de los miRNAs y factores clínicos en la detección de pacientes con riesgo de enfermedad cardiovascular aumentado

Identificador:  TDX:3106

Handle: https://hdl.handle.net/20.500.11797/TDX3106

Autors:  Taverner Torrent, Delia

Resum:
In rheumatoid arthritis (RA) there is an increased risk of cardiovascular (CV) disease compared to the general population. Ultrasonographic assessment in RA of subclinical atherosclerosis (carotid intima-media thickness (cIMT) and plaque) and arterial stiffness (pulse wave velocity (PWV), augmentation index (AIx) and distensibility) is a good marker of CV disease. MicroRNAs are independently involved in RA and CV disease and various miRNAs share a role in both pathologies. We hypothesized that a pattern of miRNAs could be identified in RA that define risk of CV disease. In our population of 214 adults with RA, we analyzed clinical-analytical and ultrasound variables, concluding that disease activity and age are differentially associated with cIMT according to gender and that age is the most important variable that determines PWV (in part a through an increase in systolic blood pressure and body mass index). In addition, we carried out a determination of the plasma expression profile of 754 miRNAs in 7 male patients with RA, in 7 male patients with early acute myocardial infarction (AMI) (before 55 years of age) without RA, and in 7 healthy male controls, detecting 10 miRNAs with similar plasma expression in patients with RA and AMI but significantly under-expressed compared to controls. In a validation study of these miRNAs on the 214 patients, we demonstrated that decreases in the expression of miR425-5p in men and of miR-451 in women are associated with high and low values of subclinical atherosclerosis, respectively. Furthermore, decreases in miR-451 expression are associated with lower arterial stiffness in our entire population. All this provides the first published evidence of a possible role of both miRNAs as useful epigenetic biomarkers to assess CV risk in patients with RA