Inflammation, thrombosis and endothelial dysfunction in myocardial infarction

Tese de doutoramento, Biologia (Fisiologia e Bioquímica), 2009, Universidade de Lisboa, Faculdade de CiênciasThe aim of this study was to investigate the association between different processes implicated in acute myocardial infarction (AMI), such as inflammation, thrombosis, immune response and endothelial dysfunction, at different phases of the disease. Thus, a follow-up of 50 AMI patients was evaluated at 3 time points: at admission before the administration of IIb/IIIa inhibitors and angioplasty, 2 days and 40 days after. A group of 25 healthy volunteers was used as reference (REF). The higher concentrations of ox-LDL at AMI onset were suggested to be related to plaque instability. Furthermore, the serial changes of ox-LDL were associated with CAD severity and eventually to lesion characteristics depending on the infarct-related artery. The results also highlight the great magnitude of the thrombotic process associated to plaque disruption at AMI onset that conceals possible variations of platelet-related thrombosis markers, mainly expressed by CD40L. Additionally, the results emphasize the importance of the inflammatory response that remains after clinical stabilization as given by the interplay of TNF-α, sICAM-1, sP-selectin, CD40L, leukocytes, NO and EMPs. Importantly, the results of sCD40L longitudinal variations allowed the differentiation of two groups of AMI patients, which also differed in NT-proBNP concentrations but did not shown variations in terms of risk factors and co-morbidities, nor influence of drug intake. This is the first study evaluating the inter-relationships between markers of inflammation, thrombosis, immune response and endothelial damage using multi-parameter longitudinal approach. The results revealed the interplay between those mechanisms and their relative importance in each phase of the disease. In conclusion, the work allowed a better understanding of the complex relationships between the studied markers involved in the different phases of AMI evolution, decisively contributing to a better understand of the pathology and mechanisms of AMI.Resumo alargado em português disponível no documentoEstudo foi co-financiado pela Fundação para a Ciência e Tecnologia (SFRHI/BD/18822/2004) através dos programas de financiamento POCI 2010 e FS

The proinflammatory soluble CD40 ligand is associated with the systemic extent of stable atherosclerosis

Funding: T.P. has received research support from Fundação para a Ciência e Tecnologia, Portugal [Project UID/BIO/04565/2020], and Programa Operacional Regional de Lisboa 2020 [Project N. 007317].Background and objectives: Polyvascular atherosclerosis is frequent and associated with a high cardiovascular risk, although the mechanisms regulating the atherosclerosis extent to single or multiple arterial territories are still poorly understood. Inflammation regulates atherogenesis and soluble CD40 ligand (sCD40L) is an inflammatory mediator associated with the presence of single-territorial atherosclerosis. We assessed whether the sCD40L expression is associated with the atherosclerosis extent to single or multiple arterial territories and with the atherosclerosis severity in different territories. Materials and Methods: We prospectively enrolled 94 participants with no atherosclerosis (controls, n = 26); isolated coronary atherosclerosis (group 1, n = 20); coronary and lower extremity (LE) atherosclerosis (group 2, n = 18); coronary and carotid atherosclerosis (group 3, n = 12); and coronary, LE, and carotid atherosclerosis (group 4, n = 18). Serum sCD40L levels were quantified. Results: The sCD40L levels (ng/mL, mean (standard deviation)) were 4.0 (1.5), 5.6 (2.6), 7.2 (4.2), 5.9 (3.7), and 5.1 (2.4) in controls and groups 1 to 4, respectively (ANOVA p = 0.012). In nonrevascularized patients, the sCD40L levels were significantly higher in group 2 than in group 1 and were correlated with the number of LE diseased segments. Prior LE bypass surgery was associated with lower sCD40L levels. Coexistence of coronary and LE atherosclerosis was independently associated with the sCD40L levels. Conclusions: The sCD40L levels were increased in stable atherosclerosis, particularly in polyvascular coronary and LE atherosclerosis. The number of LE diseased segments and prior LE revascularization were associated with sCD40L expression. To our knowledge, these are novel data, which provide insights into the mechanisms underlying multi-territorial atherosclerosis expression. sCD40L may be a promising noninvasive tool for refining the stratification of the systemic atherosclerotic burden.publishersversionpublishe

Prognostic Value of VEGF in Patients Submitted to Percutaneous Coronary Intervention

The authors gratefully acknowledge the assistance of the staff of Servico de Cardiologia, Hospital de Santa Marta, and Ms. Rute Pinheiro for the help with laboratory work. The study was financially supported by Fundacao para a Ciencia e Tecnologia, PIC/IC/82734/2007 Contract and SFRM/BPD/6308/2009 Grant, and by Liga dos Amigos do Hospital de Santa Marta.We examined the longitudinal changes of VEGF levels after percutaneous coronary intervention for predicting major adverse cardiac events (MACE) in coronary artery disease (CAD) patients. VEGF was measured in 94 CAD patients' serum before revascularization, 1-month and 1-year after. Independently of clinical presentation, patients had lower VEGF concentration than a cohort of healthy subjects (median, IQ: 15.9, 9.0-264 pg/mL versus 419, 212-758 pg/mL; P < 0.001) at baseline. VEGF increased to 1-month (median, IQ: 276, 167-498 pg/mL; P < 0.001) and remained steady to 1-year (median, IQ: 320, 173-497 pg/mL; P < 0.001) approaching control levels. Drug eluting stent apposition and previous medication intake produced a less steep VEGF evolution after intervention (P < 0.05). Baseline VEGF concentration <40.8 pg/mL conveyed increased risk for MACE in a 5-year follow-up. Results reflect a positive role of VEGF in recovery and support its importance in CAD prognosis.publishersversionpublishe

Moringa oleifera: Resource management and multiuse life tree

Moringa oleifera Lamarck (Moringaceae family) is a plant native from the Western and sub-Himalayan parts of Northwest India, Pakistan and Afghanistan. This species is widely cultivated across Africa, South-East Asia, Arabia, South America and Caribbean Islands. M. oleifera culture is also being distributed in the Semi-Arid Northeast of Brazil. It is a multiuse life tree with great environmental economic importance in industrial and medical areas. This review reports different purposes of M. oleifera including sustaining environmental resources, soil protection and shelter for animals. This plant requires not much care and distinct parts have bioactive compounds. Moringa tissues used in human and animal diets, also withdraw pollutants from water. The seeds with coagulant properties used in water treatment for human consumption, remove waste products like surfactants, heavy metals and pesticides. The oil extracted from seeds is used in cosmetic production and as biodiesel. M. oleifera tissues also contain proteins with different biological activities, including lectins, chitin-binding proteins, trypsin inhibitors, and proteases. The lectins are reported to act as insecticidal agents against Aedes aegypti (vector of dengue, chikungunya and yellow fevers) and Anagasta kuehniella (pest of stored products) and also showed water coagulant, antibacterial and blood anticoagulant activities. The presence of trypsin inhibitors has been reported in M. oleifera leaves and flowers. The inhibitor from flowers is toxic to larvae of A. aegypti. The flowers also contain caseinolytic proteases that are able to promote clotting of milk. In this sense, M. oleifera is a promising tree from a biotechnological point of view, since it has shown a great variety of uses and it is a source of several compounds with a broad range of biological activities.Conselho Nacional de Desenvolvimento Científico e Tecnológico for fellowship (LCBBC) and to the Foundation for Science and Technology, POPH/FSE (AFSS

Systemic markers of the redox balance and Apolipoprotein E Polymorphism in Atherosclerosis: the Relevance for an Integrated Study

Copyright © 2006 by Humana Press Inc.Artigo original publicado por Humana Press Inc. Actual Editora da Revista Biological Trace Element Research: Springer [A publicação original está disponível em www.springerlink.com].Prospective studies have demonstrated that an imbalance between oxidative damage and antioxidative protection can play a role in the development and progression of atherosclerosis. Also, genotypes with the apolipoprotein E ζ4 allele have been associated with an increase risk for this pathology. Based on this knowledge, the aim of this study was to evaluate indicators of the redox balance, trace elements, and apolipoprotein E allelic profile in subjects from the Lisbon population with clinically stable atherosclerosis, at risk for atherosclerotic events, and in healthy subjects for comparison. The activities of superoxide dismutase in erythrocytes and glutathione peroxidase in whole blood, plasma total thiols, and serum ceruloplasmin were kept unchanged among the three groups. Serum α-tocopherol was increased in atherosclerotic patients. Total malondialdehyde in serum and protein carbonyls in plasma, which are indicators of lipid and protein oxidative damage, respectively, reached their highest values in risk subjects. The concentrations of potassium and calcium, in plasma and in blood cells, were slightly elevated in patients and might reflect an electrolytic imbalance. Regarding the apolipoprotein E polymorphism, atherosclerotic patients had an increased incidence of the high-risk genotypes for atherogenesis (ζ3/ζ4 and ζ4/ζ4). A multivariate model applied to the general population using most of the parameters clearly separated the three groups at study (i.e., the healthy group from the steady-state group of risk disease and from the atherosclerotic one). As shown by us, the usefulness of biochemical and complementary genetic markers is warranted for a better knowledge on atherosclerosis molecular basis.Fundação para a Ciência e a Tecnologia; Centro de Biologia Ambiental; Instituto de Investigação Científica Bento da Rocha Cabral; Instituto Nacional de Saúde Dr. Ricardo Jorge

Association between mir-146a and tumor necrosis factor alpha (Tnf-α) in stable coronary artery disease

Background and Objectives: Tumor necrosis factor alpha (TNF-α) is proatherogenic and associated with the risk of acute ischemic events, although the mechanisms that regulate TNF-α expression in stable coronary artery disease (SCAD) are not fully understood. We investigated whether metabolic, inflammatory, and epigenetic (microRNA (miRNA)) markers are associated with TNF-α expression in SCAD. Materials and Methods: Patients with SCAD were prospectively recruited and their metabolic and inflammatory profiles were assessed. TNF-α levels were assessed using an enzyme-linked immunosorbent assay. The relative expression of six circulating miRNAs associated with the regulation of inflammation and/or atherosclerosis was determined. Results: Of the 24 included patients with the mean age of 65 (9) years, 88% were male, and 54% were diabetic. The TNF-α levels were (median (interquartile range)) 1.0 (0.7–1.1) pg/mL. The percentage of glycosylated hemoglobin (r = 0.418, p = 0.042), serum triglyceride levels (r = 0.429, p = 0.037), and C-reactive protein levels (r = 0.407, p = 0.048) were positively correlated with TNF-α levels. Of the candidate miRNAs, miR-146a expression levels were negatively correlated with TNF-α levels (as indicated by r = 0.500, p = 0.035 for correlation between delta cycle threshold (∆Ct) miR-146a and TNF-α levels). In multivariate analysis, serum triglyceride levels and miR-146a expression levels were independently associated with TNF-α levels. miR-146 expression levels were not associated with metabolic or other inflammatory parameters and were negatively correlated with the number of coronary vessels with obstructive disease (as indicated by r = 0.556, p = 0.017 for correlation between ∆Ct miR-146a and number of diseased vessels). Conclusions: miR-146a expression levels were negatively correlated with TNF-α levels in patients with SCAD, irrespective of other metabolic or inflammatory markers, and with the severity of coronary artery disease. The results add to the knowledge on the role of miR-146a in TNF-α-based inflammation in SCAD and support future research on the potential therapeutic use of miR-146a in such a clinical scenario.publishersversionpublishe

Blood antioxidant markers and elemental levels in Azorean patients with coronary artery disease: a preliminary study

Abstract de comunicação em Painel (3.P01) apresentada em VIIIth Conference of the International Society for Trace Element Research in Humans (ISTERH), IXth Conference of the Nordic Trace Element Society (NTES) and VIth Conference of the Helenic Trace Element Society (HTES),2007,21-26 Out, Hersonissos (Creta), GréciaAtherosclerosis (ATH) and related vascular diseases are the first cause of morbidity and mortality in Portugal, including the Azores’ Archipelago. The oxidation of low density lipoproteins (LDL) is considered to be an important event in the development of the disease. Accordingly, by preventing LDL oxidation, antioxidants can possibly reduce the risk or the progression of ATH. Essential trace elements as Cu, Se, Zn, and Fe are involved in endogenous antioxidant systems, mainly as cofactors of antioxidant enzymes. Other elements, like K and Ca, might play a role in atherogenesis while implicated in physiological and metabolic processes which are known to be disturbed in ATH. The aimof the present study was to evaluate some blood antioxidant markers and blood elemental levels in 20 Azorean subjects (ten men and ten women, aged 40 to 65 years) with coronary artery disease previously submitted to percutaneous revascularization (PCI). The whole blood gluthatione peroxidase (Se-GPx) and erythrocyte superoxide dismutase activities were measured, as well as serum vitamin E levels (by HPLC). The concentrations of K, Ca, Fe, Cu, Zn, and Se in plasma and blood cells were determined by PIXE. Results were analyzed by taking into account several cardiovascular risk factors, namely, gender, hypertension, dyslipidemia, and total plasma homocysteine (tHcy) concentration. Se-GPx activity and vitamin E levels were significantly lower (24 and 15%, respectively) in the PCI group than in controls. In blood cells, significantly differences in Ca (19±5 vs 24±6 μg/mL) and Zn (14±1 vs 12±2 μg/mL) levels were observed in PCI women (but not in men) compared to the respective counterparts. Also in PCI women, both serum triglyceride and plasma tHcy concentrations were above reference values and higher than in men. Results suggest a decreased antioxidant status in PCI patients. In particular, women appear to be less protected than men, as reflected in some cardiovascular risk factors