👤 Antonio José López-Farré

Although BRCA1 gene mutations have been associated with breast cancer, BRCA1 mutations have been also involved in other functions. Thrombosis and coagulation are novel mechanisms recently associated with cancer. The aims of the present study were (a) to evaluate, using proteomics, if BRCA1 mutation carriers have a different plasma proteins expression related to thrombosis and coagulation profile than non-mutant BRCA1 women and (b) to analyze if the expression of these proteins may be different among BRCA1 mutation carriers with and without breast cancer. Proteomic study was based on 2-dimensional electrophoresis and mass spectrometry. The study was performed in 10 BRCA1 non-mutant controls and 21 women with BRCA1 mutations (with breast cancer (n = 8) and breast cancer-free (n = 13)), all of them free of family history or diagnosis of ovarian cancer. Proteomic study showed that fibrinogen gamma chain isotypes 2 and 3, serotransferrin isotype 4, and convertase C3/C5 isotypes 1-5 were significantly increased in plasma from BRCA1 mutation carriers with respect to BRCA1 non-mutant controls. Plasma levels of alpha-1 antitrypsin isotypes 2-5, apolipoprotein A-IV, and vitamin D-binding protein isotypes 1 and 2 were significantly reduced in BRCA1 mutation carriers with respect to non-mutant controls. Only apolipoprotein A-IV plasma levels were significantly higher in cancer-free BRCA1 mutations carriers compared with BRCA1 mutations carriers who developed breast cancer. It is suggested that independently of breast cancer generation, BRCA1-encoded gene alterations are associated with changes in the expression of circulating proteins associated with thrombosis and coagulation. Show less

The aim of this study was to analyze the effect of 2 antiplatelet regimens on the inhibition of GP IIb/IIIa-dependent platelet activation and their association with the poststenting inflammatory response. Seventeen patients with acute myocardial infarction were divided into 2 groups: (A) clopidogrel plus tirofiban infusion administered together during inclusion (n = 10); (B) clopidogrel administered at inclusion and followed 2 hours after by tirofiban (n = 7). Blood samples were obtained at inclusion and at 24 and 48 hours after stenting. Before stenting, a greater reduction of GP IIb/IIIa-dependent platelet activation was found in both groups, although it was greater in group A than in group B. This statistical difference was not observed at 24 and 48 hours after the procedure. At 48 hours after stenting, interleukin-6, interleukin-10, soluble intracellular adhesion molecule-1, and soluble CD40 ligand plasma values were not different between experimental groups. By proteomics, different isoforms of the following proteins were identified: alpha 1-antitrypsin (ATT-1), fibrinogen gamma chain, apolipoprotein A-IV, apolipoprotein A-I, vitamin D binding protein, haptoglobin, and serotransferrin. At 48 hours after stenting, only the plasma expression of the ATT-1 isoform 5 was significantly increased in group A compared with group B. In conclusion, a greater inhibition of GP IIb/IIIa-dependent platelet activation before stenting was not correlated with a different inflammatory activity early after stenting. Show less

Proteomics is a technology to detect and identify several proteins and their isoforms in a single sample. We used proteomics to analyze modifications in the protein map of plasma after simvastatin treatment of moderate hypercholesterolemic patients. Plasma from hypercholesterolemic patients (n = 9) was compared before and after 12 weeks of simvastatin treatment (40 mg/day). Patients with similar cardiovascular risk factors were used as controls (CR group). By using two-dimensional electrophoresis and mass spectrometry, we identified the different protein isoforms. The plasma expression of three fibrinogen gamma chain isoforms (FGG) was enhanced, whereas the expression of two isoforms of the fibrinogen beta chain (FGB) was reduced in the hypercholesterolemic patients compared with the CR group. The expression of apolipoprotein A-IV and three haptoglobin isoforms was higher in hypercholesterolemic patients. Simvastatin treatment modified the plasma expression of FGG chain isoform 1, FGB chain isoforms 1 and 2, vitamin D binding protein isoform 3, apo A-IV, and haptoglobin isoform 2. The modification of FGG chain isoform 1 and FGB chain isoforms 1 and 2 was positively correlated with total plasma cholesterol level. Proteomic analysis of plasma may help to know more in depth the molecular mechanism modified by simvastatin treatment. Show less