Proteins Involved in Platelet Signaling Are Differentially Regulated in Acute Coronary Syndrome: A Proteomic Study

BACKGROUND: Platelets play a fundamental role in pathological events underlying acute coronary syndrome (ACS). Because platelets do not have a nucleus, proteomics constitutes an optimal approach to follow platelet molecular events associated with the onset of the acute episode. METHODOLOGY/PRINCIPAL FINDINGS: We performed the first high-resolution two-dimensional gel electrophoresis-based proteome analysis of circulating platelets from patients with non-ST segment elevation ACS (NSTE-ACS). Proteins were identified by mass spectrometry and validations were by western blotting. Forty protein features (corresponding to 22 unique genes) were found to be differentially regulated between NSTE-ACS patients and matched controls with chronic ischemic cardiopathy. The number of differences decreased at day 5 (28) and 6 months after the acute event (5). Interestingly, a systems biology approach demonstrated that 16 of the 22 differentially regulated proteins identified are interconnected as part of a common network related to cell assembly and organization and cell morphology, processes very related to platelet activation. Indeed, 14 of those proteins are either signaling or cytoskeletal, and nine of them are known to participate in platelet activation by αIIbβ3 and/or GPVI receptors. Several of the proteins identified participate in platelet activation through post-translational modifications, as shown here for ILK, Src and Talin. Interestingly, the platelet-secreted glycoprotein SPARC was down-regulated in NSTE-ACS patients compared to stable controls, which is consistent with a secretion process from activated platelets. CONCLUSIONS/SIGNIFICANCE: The present study provides novel information on platelet proteome changes associated with platelet activation in NSTE-ACS, highlighting the presence of proteins involved in platelet signaling. This investigation paves the way for future studies in the search for novel platelet-related biomarkers and drug targets in ACS

Management and 1-year outcomes of patients with newly diagnosed atrial fibrillation and chronic kidney disease: Results from the prospective garfield-af registry

Background-—Using data from the GARFIELD-AF (Global Anticoagulant Registry in the FIELD–Atrial Fibrillation), we evaluated the impact of chronic kidney disease (CKD) stage on clinical outcomes in patients with newly diagnosed atrial fibrillation (AF). Methods and Results-—GARFIELD-AF is a prospective registry of patients from 35 countries, including patients from Asia (China, India, Japan, Singapore, South Korea, and Thailand). Consecutive patients enrolled (2013–2016) were classified with no, mild, or moderate-to-severe CKD, based on the National Kidney Foundation’s Kidney Disease Outcomes Quality Initiative guidelines. Data on CKD status and outcomes were available for 33 024 of 34 854 patients (including 9491 patients from Asia); 10.9% (n=3613) had moderate-to-severe CKD, 16.9% (n=5595) mild CKD, and 72.1% (n=23 816) no CKD. The use of oral anticoagulants was influenced by stroke risk (ie, post hoc assessment of CHA2DS2-VASc score), but not by CKD stage. The quality of anticoagulant control with vitamin K antagonists did not differ with CKD stage. After adjusting for baseline characteristics and antithrombotic use, both mild and moderate-to-severe CKD were independent risk factors for all-cause mortality. Moderate-to-severe CKD was independently associated with a higher risk of stroke/systemic embolism, major bleeding, new-onset acute coronary syndrome, and new or worsening heart failure. The impact of moderate-to-severe CKD on mortality was significantly greater in patients from Asia than the rest of the world (P=0.001). Conclusions-—In GARFIELD-AF, moderate-to-severe CKD was independently associated with stroke/systemic embolism, major bleeding, and mortality. The effect of moderate-to-severe CKD on mortality was even greater in patients from Asia than the rest of the world

The Effectiveness of a Program of Physical Activity and Diet to Modify Cardiovascular Risk Factors in Patients with Severe Mental Illness (CAPiCOR Study)

Background: Patients with severe mental disorders have a higher prevalence of cardiovascular risk factors. Obesity and sedentarism are cardiovascular risk factors and their control reduces morbidity and mortality. Thus, interventions directed toward decreasing weight and/ or increasing the level of physical activity are necessary.Objectives: The aim of this study would be to evaluate the effectiveness of an educational intervention focused on diet and physical activity in order to change the amount of physical activity, Body Mass Index and waist circumference in these patients.Design: Randomized clinical trial with a control group with one-year follow-up.Setting: Outpatient Mental Health Teams of Barcelona and a residence for patients with severe mental disorders.Participants: Patients between 18 and 65 years of age diagnosed with schizophrenia, a schizoaffective disorder or bipolar disorder in treatment with antipsychotic medication and a low level of physical activity (240 patients in each randomized group).Intervention group: Physical activity group educational program of 24 sessions over 12 weeks and diet (16 sessions in the fist 8 weeks) carried out by nurses and physical activity specialists.Control group: Usual practice with regular checks and the usual treatment of their disease.Main outcome measures: Level of physical activity (IPAQ questionnaire), weight, Body Mass Index and waist circumference.Other outcomes: Cardiovascular risk, quality of life (SF-36 questionnaire), tobacco consumption, dietary habit (PREDIMED questionnaire), blood pressure and laboratory parameters (cholesterol, triglycerides, glucose).Evaluations will be masked and will be made at 0, 3, 6 and 12 months.Data analysis: Intention to treat analysis. Analysis of variance for repeated measures to adjust for differences attributable to the effect of the intervention for potential confounders (drug treatment, care level of intervention and mental status of the patient).Ethical aspects: The project has been evaluated and approved by the ethics committee (CEIC) of the Primary Healthcare-University Research Institute IDIAP Jordi Gol, with registration number P11/64.Trial registration: Clinicaltrials.gov NCT01729650

Oxidative signature of cerebrospinal fluid from mild cognitive impairment and Alzheimer disease patients

Background: Several studies suggest that pathological changes in Alzheimer’s disease (AD) brain begin around 10–20 years before the onset of cognitive impairment. Biomarkers that can support early diagnosis and predict development of dementia would, therefore, be crucial for patient care and evaluation of drug efficacy. Although cerebrospinal fluid (CSF) levels of Aβ42, tau, and p-tau are well-established diagnostic biomarkers of AD, there is an urgent need to identify additional molecular alterations of neuronal function that can be evaluated at the systemic level. Objectives: This study was focused on the analysis of oxidative stress-related modifications of the CSF proteome, from subjects with AD and amnestic mild cognitive impairment (aMCI). Methods: A targeted proteomics approach has been employed to discover novel CSF biomarkers that can augment the diagnostic and prognostic accuracy of current leading CSF biomarkers. CSF samples from aMCI, AD and control individuals (CTR) were collected and analyzed using a combined redox proteomics approach to identify the specific oxidatively modified proteins in AD and aMCI compared with controls. Results: The majority of carbonylated proteins identified by redox proteomics are found early in the progression of AD, i.e., oxidatively modified CSF proteins were already present in aMCI compared with controls and remain oxidized in AD, thus suggesting that dysfunction of selected proteins initiate many years before severe dementia is diagnosed. Conclusions: The above findings highlight the presence of early oxidative damage in aMCI before clinical dementia of AD is manifested. The identification of early markers of AD that may be detected peripherally may open new prospective for biomarker studie