Person: Zamorano León, José Javier
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First Name
José Javier
Last Name
Zamorano León
Affiliation
Universidad Complutense de Madrid
Faculty / Institute
Medicina
Department
Salud Pública y Materno-Infantil
Area
Medicina Preventiva y Salud Pública
Identifiers
6 results
Search Results
Now showing 1 - 6 of 6
Item Platelet Content of Nitric Oxide Synthase 3 Phosphorylated At Serine1177 Is Associated with the Functional Response of Platelets to Aspirin(PLoS ONE, 2013) Modrego, Javier; Azcona, Luis; Martín Palacios, Naiara; Zamorano León, José Javier; Segura, Antonio; Rodriguez, Pablo; Guerra, Reddy; Tamargo Menéndez, Juan; Macaya Miguel, Carlos; López Farre, Antonio JoséObjective: To analyse if platelet responsiveness to aspirin (ASA) may be associated with a different ability of platelets to generate nitric oxide (NO). Patients/methods: Platelets were obtained from 50 patients with stable coronary ischemia and were divided into ASA-sensitive (n = 26) and ASA-resistant (n = 24) using a platelet functionality test (PFA-100). Results: ASA-sensitive platelets tended to release more NO (determined as nitrite + nitrate) than ASA-resistant platelets but it did not reach statistical significance. Protein expression of nitric oxide synthase 3 (NOS3) was higher in ASA-sensitive than in ASA-resistant platelets but there were no differences in the platelet expression of nitric oxide synthase 2 (NOS2) isoform. The highest NOS3 expression in ASA-sensitive platelets was independent of the presence of T-to-C mutation at nucleotide position -786 (T(-786) → C) in the NOS3-coding gene. However, platelet content of phosphorylated NOS3 at Serine (Ser)(1177), an active form of NOS3, was higher in ASA-sensitive than in ASA-resistant platelets. The level of platelet NOS3 Ser(1177) phosphorylation was positively associated with the closure time in the PFA-100 test. In vitro, collagen failed to stimulate the aggregation of ASA-sensitive platelets, determined by lumiaggregometry, and it was associated with a significant increase (p = 0.018) of NOS3 phosphorylation at Ser(1177). On the contrary, collagen stimulated the aggregation of ASA-resistant platelets but did not significantly modify the platelet content of phosphorylated NOS3 Ser(1177). During collagen stimulation the release of NO from ASA-sensitive platelets was significantly enhanced but it was not modified in ASA-resistant platelets. Conclusions: Functional platelet responsiveness to ASA was associated with the platelet content of phosphorylated NOS3 at Ser(1177).Item Plasma desmoplakin I biomarker of vascular recurrence after ischemic stroke(Journal of Neurochemistry, 2012) López Farre, Antonio José; Zamorano León, José Javier; Segura, Antonio; Jiménez Mateos Cáceres, Petra; Modrego, Javier; Rodriguez Sierra, Pablo; Calatrava, Laura; Tamargo Menéndez, Juan; Macaya Miguel, CarlosStroke patients have a high risk of vascular recurrence. Biomarkers related to vascular recurrence, however, remain to be identified. The aim of the study was to identify, through proteomic analysis, plasma biomarkers associated with vascular recurrence within one year after the first ischemic stroke. This is a substudy (n = 134) of a large prospective multicenter study of post-stroke patients with an ischemic stroke. Plasma samples were obtained at inclusion. Among the identified proteins, only plasma levels of desmoplakin I were associated with protection against a new vascular event (Odds ratio: 0.64; 95% CI: 0.46-0.89; p = 0.009) after adjustment for hypercholesterolemia, statins and previous atherothrombotic stroke subtype. A greater number of patients without vascular recurrence had been treated with statins within three months of the recent ischemic stroke. Only patients who had been taking statins for 3 months after the ischemic stroke and did not suffer vascular recurrence over a follow-up year, have higher levels of desmoplakin I at the time of inclusion (Odds ratio 0.49; 95% CI: 0.28-0.86; p = 0.013). Increased desmoplakin I levels, determined within 1-3 months of the first ischemic stroke, could be a biomarker for statin responsiveness against a new vascular event in post-ischemic stroke patients taking statins early (1-3 months) after the ischemic stroke.Item Impact of Clopidogrel and Aspirin Treatment on the Expression of Proteins in Platelets from Type-2 Diabetic Patients with Stable Coronary Ischemia(Journal of Pharmaceutical Sciences, 2012) Azcona, Luis; López Farre, Antonio José; Jiménez Mateos Cáceres, Petra; Segura, Antonio; Rodríguez Sierra, Pablo; Modrego, Javier; Zamorano León, José Javier; Macaya Miguel, CarlosThe purpose of this study was to compare the effect of dual antiplatelet therapy [clopidogrel + aspirin (ASA)] with respect to ASA on the protein expression of platelets from controlled type-2 diabetic patients with stable coronary ischemia. Patients had been taking ASA (100 mg day) and they were randomized to receive (n = 29) or not (n = 28) 75 mg day clopidogrel for 12 ± 2 weeks in a blind form. Protein expression was analyzed by two-dimensional electrophoresis and mass spectrometry. The protein expression of a limited number of proteins such as actin-binding protein isotypes 2 and 5, lactate dehydrogenase, serotransferrin isotype 4, protein disulfide isomerase-A3 isotype 1, fibrinogen beta chain isotype 5, Ras-related protein Rab-7b isotypes 1 and 6, and immunoglobulin heavy chain was changed after dual antiplatelet therapy. Plasma level of platelet factor 4 (PF4), an in vivo marker of platelet activity, was not different between both groups. These changes suggest lower platelet reactivity after dual antiplatelet therapy in the studied patients. However, the variation in platelet proteome was lower than it would be initially expected, taking into account the apparent clinical beneficial effects of dual antiplatelet therapy. PF4 plasma level was not further decreased in the platelets treated for a longer time than 9-12 months with ASA + clopidogrel, as compared with ASA alone.Item New circulating biomarkers for predicting cardiovascular death in healthy population(Journal of Cellular and Molecular Medicine, 2015) Olle, Melander; Modrego, Javier; Zamorano León, José Javier; Santos Sancho, Juana María; Lahera Julia, Vicente; López Farre, Antonio JoséThere is interest to analyse newer biomarkers to identify healthy individuals at risk to develop cardiovascular disease (CVD) incidents and death. To determine in healthy individuals new circulating protein biomarkers, whose systemic levels may be associated with the risk of future development of CVD incidents and death. The study was performed in 82 individuals from the Malm€o Diet and Cancer study cohort, free from CVD of whom 41 developed CVD and 41 did not. Plasma proteins related to inflammation and thrombo-coagulating processes were analysed. a1-antitrypsin isotype 3 plasma levels were significantly higher while apolipoprotein J plasma levels were lower in participants that developed CVD incidents than those that did not develop acute cardiovascular episode. Of 82 participants, 17 died by CVD causes. There were proteins whose expression in plasma was significantly higher in participants suffering CVD death as compared with those that did not die by CVD. These proteins included: fibrinogen b-chain isotypes 1 and 3, fibrinogen-c-chain isotype 2, vitamin D-binding protein isotypes 1, 2 and 3, a1-antitrypsin isotypes 3 and 6, haptoglobin isotypes 3,4,5 and 5, haemopexin isotypes 1 and 2, and Rho/Rac guanine nucleotide exchange factor 2. Moreover, apolipoprotein J plasma levels were found lower in participants that died by cardiovascular cause. Association between plasma levels of proteins and CVD death was independent of age, gender, conventional risk factors and plasma C-reactive protein levels. Several protein plasma levels and protein isotypes related to inflammation and thrombo-coagulating phenomena were independently associated with the risk of future CVD death.Item Proteomic changes related to ‘‘bewildered’’ circulating platelets in the acute coronary syndrome(Proteomics, 2011) López Farre, Antonio José; Zamorano León, José Javier; Azcona, Luis; Modrego, Javier; Mateos Cáceres, Petra J.; González Armengol, Juan Jorge; Villaroel, Pedro; Moreno Herrero, Rosario; Rodríguez Sierra, Pablo; Segura, Antonio; Tamargo Menéndez, Juan; Macaya Miguel, CarlosAcute coronary syndromes (ACS) are associated with platelet activation. The aim of the present study was to study the protein expression level associated with glycolysis, oxidative stress, cytoskeleton and cell survival in platelets obtained during an ACS. Platelets from 42 coronary ischemic patients, divided into patients admitted within 24 h after the onset of chest pain (ACS group; n=16) and patients with stable coronary ischemic disease (CAD, n=26), were analyzed using proteomics. The expression levels of proteins involved in cellular cytoskeleton (F-actin capping, β-tubulin, α-tubulin isotypes 1 and 2, vinculin, vimentin and two Ras-related protein Rab-7b isotypes), glycolysis pathway (glyceraldehyde-3-phosphate dehydrogenase, lactate dehydrogenase and two pyruvate kinase isotypes) and cellular-related antioxidant system (manganese superoxide dismutase) and even the expression and activity of glutathione-S-transferase were significantly reduced in platelets from ACS patients compared to CAD patients. Moreover, reduction in the expression of proteins associated with cell survival such as proteasome subunit β type 1 was also observed in ACS platelets compared with CAD platelets. Principal component and logistic regression analysis suggested the existence of factors (proteins) expressed in the platelets inversely associated with acute coronary ischemia. In summary, these results suggest the existence of circulating antioxidant, cytoskeleton and glycolytic-“bewildered” platelets during the acute phase of a coronary event.Item Case report of a Spanish patient with arrhythmogenic right ventricular cardiomyopathy and palmoplantar keratoderma without plakoglobin and desmoplakin gene modifications(International Journal of Cardiology, 2007) Alonso Orgaz, S; Zamorano León, José Javier; Fernández Arquero, Miguel; Pérez Villacastín Domínguez, Julián; Perez-Castellano, N; García Torrent, María Jesús; Macaya Miguel, Carlos; López Farre, Antonio JoséWe report a case of a 43 year old man from Spain, who has been diagnosed with Naxos disease. It is a hereditary disorder characterized by palmoplantar keratoderma, woolly hair and cardiomyopathy, which has been associated with a mutation in plakoglobin encoding gene in chromosome 17q21. In the patient, the direct sequencing of the plakoglobin gene discarded TG deletion at 2157 characteristic of Naxos disease. Analysis of the reported desmoplakin mutations associated with Carvajal Syndrome, another ARVC disease, that it is also accompanied with a skin and hair disorder, also failed to reveal mutations in desmoplakin gene. These results suggest the existence of other causative genes and/or other putative sites in desmoplakin/plakoglobin encoding genes than those recently published.