Search

Jesús Beltrán-García,1– 3 Rebeca Osca-Verdegal,1,3 Daniel Pérez-Cremades,2,3 Susana Novella,2,3 Carlos Hermenegildo,2,3 Federico V Pallardó,1– 3 José Luis García-Giménez1– 3 1Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, Madrid, Spain; 2Instituto de Investigación Sanitaria INCLIVA, Valencia, Spain; 3Departamento de Fisiología, Facultad de Medicina y Odontología, Universitat de València, València, SpainCorrespondence: José Luis García-Giménez, Departamento de Fisiología, Facultad de Medicina y Odontología, Universitat de València, València, 46010, Spain, Tel +34 963 864 646, Email j.luis.garcia@uv.esIntroduction: Circulating extracellular histones acquire relevance as cytotoxic mediators in sepsis. Extracellular histones act as damage-associated molecular patterns (DAMPs), which induce oxidative stress and NLRP3 inflammasome activation. Inflammasome mediates pyroptosis, a programmed cell death mechanism that produces inflammation. Despite evidence for inflammasome activation in immune cells during sepsis, it was unknown whether extracellular histones can produce endothelial inflammasomes activation.Methods: We used human umbilical vein endothelial cells (HUVEC) to explore the activation of pyroptosis, endothelial function and inflammation by extracellular histones. We evaluated pyroptosis by flow cytometry, caspase-1 activity assay, and gene and protein expression analysis by RT-qPCR and Western blot, respectively. The upstream molecular responses involved in pyroptosis activation by extracellular histones were validated by means of using antioxidant glutathione ethyl ester and NLRP3 inflammasome inhibitors. Finally, using mass spectrometry, we measured circulating histones in blood from critically-ill patients and demonstrated that circulating histone levels correlated with the expression of pyroptosis-related cytokines, the release of endothelial adhesion factors and septic shock severity.Results: We found that extracellular histones mediate the activation of NLRP3 inflammasome and pyroptosis in endothelial cells by contributing to endothelial dysfunction and the dysregulation of the immune response mediated by endothelium. Likewise, we demonstrated how the hyperacetylation of extracellular histones or the use of antioxidants decreased pyroptosis. In addition, we showed that pyroptosis is a feasible process occurring in septic shock patients.Discussion: Circulating histone levels correlated with the expression of pro-inflammatory and pyroptosis-related cytokines, the release of endothelial adhesion factors and septic shock severity. We propose to block histone-mediated pyroptosis as a feasible therapeutic strategy in sepsis.Graphical Abstract: Keywords: sepsis, extracellular histones, histone acetylation, endothelium, inflammasome, NLRP3

Extracellular histones have been reported to aggravate different pathophysiological processes by increasing vascular permeability, coagulopathy, and inflammation. In the present study, we elucidate how extracellular histones (10–100 µg/mL) concentration dependently increase cytosolic reactive oxygen species (ROS) production using human umbilical vein endothelial cells (HUVECs). Furthermore, we identify cyclooxygenase (COX) and NADPH oxidase (NOX) activity as sources of ROS production in extracellular histone-treated HUVEC. This COX/NOX-mediated ROS production is also involved in enhanced NF-kB activity and cell adhesion molecules (VCAM1 and ICAM1) expression in histone-treated HUVEC. Finally, by using different toll-like receptor (TLR) antagonists, we demonstrate the role of TLR4 in CAMs overexpression triggered by extracellular histones in endothelial cells. In conclusion, our data suggest that through TLR4 signaling, extracellular histones increase endothelial cell activation, a mechanism involving increased COX- and NOX-mediated ROS. These findings increase our understanding on how extracellular histones enhance systemic inflammatory responses in diseases in which histone release occurs as part of the pathological processes.

The role of sex in cardiovascular physiology has been extensively studied and has a great impact on the pathophysiology of cardiovascular diseases (CVD). In the last years, epigenetic regulation of gene expression has been established as a new mechanism for the correct cardiovascular homeostasis, involving both sex chromosomes and sex hormones. A number of epigenetic modifiers are encoded on sex chromosomes, which can induce sex differences in somatic gene expression independently of hormonal differences. Otherwise, sex hormones are transcriptional regulators in their own right by acting as ligands for nuclear hormone receptors and therefore providing the phenotype of sex-associated gene expression. Thus, this chapter summarizes epigenetic mechanisms concerning CVD, in particular DNA methylation, histone modifications, and noncoding RNA related to sex chromosomes and sex hormones. We conclude that epigenetic mechanisms can also modulate the differential gene expression between men and women, contributing to the marked sex differences found in CVD. However, our understanding of sex differences at the molecular level is limited due to the scarcity of sex stratification in preclinical and translational cardiovascular epigenetics. An adjustment to our approaches needs to be made to gain a more detailed understanding of sex differences, necessary to discover new sex-specific downstream nodes in classical signaling pathways.

O desenvolvimento e o bem-estar das sociedades industrializadas obrigam à inevitável convivência com matérias perigosas. Encontramo-las nos diversos estados físicos, em condições de pressão e temperatura muito distintas, armazenadas dentro de unidades industriais e espaços comerciais com caraterísticas distintas, nas mais variadas vias de comunicação convencionais ou nas condutas de transporte implantadas ao longo do território, contribuindo, significativamente, para a sua dispersão territorial. Este estudo refere-se, exclusivamente, à área do município de Mortágua. Pretendeu-se com ele proceder ao levantamento das infraestruturas que suportam o transporte de matérias perigosas, o tipo de matérias perigosas que nelas circulam e a sua frequência de transporte. Posteriormente, recorreu-seao software ALOHA® para simular a ocorrência de um acidente em cada infraestrutura, motivando três situações distintas: a propagação de uma nuvem tóxica, de uma nuvem inflamável e da radiação térmica provocada por BLEVE ou Jet Fire. Os resultados obtidos confirmam a falta de informação relativa a alguns tipos de transporte de matérias perigosas e, quando existe, não está tratada de forma adequada.

This paper focuses on the susceptibility evaluation to bank gullies on earthen embankments through the application of SIMWE (SIMulated Water Erosion) model, using a high resolution digital elevation model (1 meter spatial resolution). The results provided by the model are compared with the hydrologic characteristics, soil texture and soil structure of the agricultural terraces. This approach demonstrates an association between the spatial distribution of erosive forms with high values of water depth and reduced water discharge that are consistent with the lower values of electrical resistivity. The areas with the highest percentage of erosive forms, related to sediment flux, transport capacity and sediment concentration susceptibility, assume medium values. These figures, combined with a low hydraulic conductivity and soil infiltration capacity, are consistent with the fine texture of soils, allowing increased runoff and the development of linear erosion.

Women show a lower incidence of cardiovascular diseases than age-matched men, but this benefit disappears after menopause. Oestrogen-mediated vascular actions are mainly attributed to oestradiol and exerted by oestrogen receptors (ERα, ERβ and G protein-coupled oestrogen receptor), through rapid and/or genomic mechanisms, but these effects depend on ageing and inflammation. A cardiovascular approach in women's health has arisen due to controversy regarding oestrogen's beneficial impact as reported in experimental and observational studies and large randomized trials. These can be explained, in part, by two mutually non-exclusive hypotheses. On the one hand, the timing hypothesis, which states that oestrogen-mediated benefits occur before the detrimental effects of ageing are established in the vasculature; on the other hand, ageing and/or hormonal-associated changes in ER expression that could lead to a deleterious imbalance in favour of ERβ over ERα, generally associated with higher inflammation and endothelial dysfunction. In experimental studies, oestradiol acting on ERα promotes the release of vasoactive compounds such as nitric oxide (NO) and prostacyclin, and shifts the angiotensin axis towards angiotensin 1-7 production. Mechanisms underlying oestradiol vascular function also include anti-inflammatory and epigenetic modifications. 17β-Oestradiol changes the transcriptomic profile of endothelial cells, and the involvement of miRNA in the regulatory pathways of vascular function reinforces assumptions regarding the vascular actions of oestrogen. Thus, the present Symposium Review aims to postulate the role of ERα in oestrogen modulation of endothelium-derived mediators and vascular physiology, as well as its relationship with miRNA and inflammation, and elucidate how physiological changes in postmenopausal women counteract the observed effects.

Aims Endothelial progenitor cells (EPC) play a role in endothelium integrity maintenance and regeneration. Decreased numbers of EPC or their impaired function correlates with an increase in cardiovascular events. Thus, EPC are important predictors of cardiovascular mortality and morbidity. Microparticles carrying Sonic hedgehog (Shh) morphogen (MPShh+) trigger pro-angiogenic responses, both in endothelial cells and in ischaemic rodent models. Here, we propose that MPShh+ regulates EPC function, thus enhancing vasculogenesis, and correcting the defects in dysfunctional EPC obtained from acute myocardial infarction (AMI) patients. Methods and results The mechanisms underlying Shh pathway function and nitric oxide (NO) production in EPC were evaluated. MPShh+ increased both the in vitro and in vivo vasculogenic capacity of EPC isolated from adult human peripheral blood samples. MPShh+ treatment significantly increased the expression of Shh signalling pathway genes (PTCH1, SMO, and GLI1) and masters of pro-angiogenic genes (NOS3, VEGFA, KDR, and KLF2) in EPC. Moreover, MPShh+ increased both the protein expression and activity of eNOS, resulting in increased NO production. Most importantly, MPShh+ improved the vasculogenic capacity of EPC from AMI patients to levels similar to that of EPC from healthy patients. All these effects were due to the activation of Shh pathway. Conclusion MPShh+ increase both the vasculogenesis of EPC and their capacity to produce NO, including EPC from patients who have recently suffered an AMI. This study emphasizes MPShh+ and EPC as potential therapeutic tools for improving vascular regeneration as a treatment for cardiovascular ischaemic disease.

Women can be considered hemodynamically younger than men of the same age, based on epidemiological studies establishing that the incidence of vascular diseases in women is relatively lower compared to that in aged-matched men. However, after menopause, these numbers increase to values that are close to those found in men. Vascular ageing is associated with structural and functional changes of the vascular wall, including endothelial dysfunction, arterial stiffening, and remodelling, as well as impaired angiogenesis, which become major risk factors in the development of cardiovascular disease.

Intracellular renin-angiotensin system (RAS) can operate independently of the circulating RAS. Estrogens provide protective effects by modulating the RAS. Our aim was to investigate the effect of estradiol (E2) on angiotensin converting enzymes (ACE) 1 and ACE2 expression and activities in human endothelial cells (HUVEC), and the role of estrogen receptors (ER). The results confirmed the presence of active intracellular RAS in HUVEC. Physiological concentrations of E2 induced a concentration-dependent increase of ACE1 and ACE2 mRNA expression and ACE1, but not ACE2, protein levels. ACE1 and ACE2 enzymatic activities were also induced with E2. These effects were mediated through ERα activation, since ER antagonists ICI 182780 and MPP completely abolished the effect of E2. Moreover, the ERα agonist PPT mirrored the E2 effects on ACE1 and ACE2 protein expression and activity. Exposure of endothelial cells to E2 significantly increased Ang-(1–7) production. In conclusion, E2 increases Ang-(1–7) production, through ERα, involving increased ACE1 and ACE2 mRNA expression and activity and ACE1 protein levels. Fil: Mompeón, Ana. Universidad de Valencia; España Fil: Lázaro Franco, Macarena. Universidad de Valencia; España Fil: Bueno Betí, Carlos. Universidad de Valencia; España Fil: Pérez Cremades, Daniel. Universidad de Valencia; España Fil: Vidal Gómez, Xavier. Universidad de Valencia; España Fil: Monsalve, Elena. Universidad de Valencia; España Fil: Gironacci, Mariela Mercedes. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Biológica; Argentina Fil: Hermenegildo, Carlos. Universidad de Valencia; España Fil: Novella, Susana. Universidad de Valencia; España

Circulating histones have been proposed as targets for therapy in sepsis and hyperinflammatory symptoms. However, the proposed strategies have failed in clinical trials. Although different mechanisms for histone-related cytotoxicity are being explored, those mediated by circulating histones are not fully understood. Extracellular histones induce endothelial cell death, thereby contributing to the pathogenesis of complex diseases such as sepsis and septic shock. Therefore, the comprehension of cellular responses triggered by histones is capital to design effective therapeutic strategies. Here we report how extracellular histones induce autophagy and apoptosis in a dose-dependent manner in cultured human endothelial cells. In addition, we describe how histones regulate these pathways via Sestrin2/AMPK/ULK1-mTOR and AKT/mTOR. Furthermore, we evaluate the effect of Toll-like receptors in mediating autophagy and apoptosis demonstrating how TLR inhibitors do not prevent apoptosis and/or autophagy induced by histones. Our results confirm that histones and autophagic pathways can be considered as novel targets to design therapeutic strategies in endothelial damage.

Cardiovascular diseases are a worldwide health problem and are the leading cause of mortality in developed countries. Together with experimental data, the lower incidence of cardiovascular diseases in women than in men of reproductive age points to the influence of sex hormones at the cardiovascular level and suggests that estrogens play a protective role against cardiovascular disease and that this role is also modified by ageing. Estrogens affect cardiovascular function via their specific estrogen receptors to trigger gene expression changes at the transcriptional level. In addition, emerging studies have proposed a role for microRNAs in the vascular effects mediated by estrogens. miRNAs regulate gene expression by repressing translational processes and have been estimated to be involved in the regulation of approximately 30% of all protein-coding genes in mammals. In this review, we highlight the current knowledge of the role of estrogen-sensitive miRNAs, and their influence in regulating vascular ageing.

The beneficial effects of estrogen on the cardiovascular system have been reported extensively. In fact, the incidence of cardiovascular diseases in women is lower than in age-matched men during their fertile stage of life, a benefit that disappears after menopause. These sex-related differences point to sexual hormones, mainly estrogen, as possible cardiovascular protective factors. The regulation of vascular function by estrogen is mainly related to the maintenance of normal endothelial function and is mediated by both direct and indirect gene transcription through the activity of specific estrogen receptors. Some of these mechanisms are known, but many remain to be elucidated. In recent years, microRNAs have been established as non-coding RNAs that regulate the expression of a high percentage of protein-coding genes in mammals and are related to the correct function of human physiology. Moreover, within the cardiovascular system, miRNAs have been related to physiological and pathological conditions. In this review, we address what is known about the role of estrogen-regulated miRNAs and their emerging involvement in vascular biology.

Background Frailty predicts mortality after acute coronary syndrome (ACS). The standard frailty scales, such as the Fried score, consist of a variety of questionnaires and physical tests. Our aim was to investigate easily available clinical data and blood markers to predict frailty at discharge, in elderly patients after ACS. Methods A total of 342 patients older than 65 years, survivors after ACS, were included. A high number of clinical variables were collected. In addition, blood markers potentially linked to frailty and related to the processes of inflammation, coagulation, hormonal dysregulation, nutrition, renal dysfunction, and heart dysfunction were determined. Frailty was evaluated using the Fried score at discharge. The main outcome was frailty defined by a Fried score ≥ 3 points. Secondary endpoints were mortality and myocardial infarction at 30-month median follow-up. Results A total of 116 patients were frail. Seven clinical variables or biomarkers predicted frailty: age ≥ 75 years, female, prior ischemic heart disease, admission heart failure, haemoglobin ≤ 12.5 g/dL, vitamin D ≤ 9 ng/mL, and cystatin-C ≥ 1.2 mg/L. This model based on clinical data and biomarkers showed an excellent discrimination accuracy for frailty (C-statistic = 0.818). During the follow-up, 105 patients died and 137 died or suffered myocardial infarction. The clinical data and biomarker model (C-statistics = 0.730 and 0.691) performed better than the Fried score (C-statistics = 0.676 and 0.650) for death and death or myocardial infarction, respectively. Conclusions Easy available clinical data and biomarkers can identify frail patients at discharge after ACS and predict outcomes better than the standard Fried's frailty scale.

The mobilization pattern and functionality of endothelial progenitor cells after an acute ischemic event remain largely unknown. The aim of our study was to characterize and compare the short- and long-term mobilization of endothelial progenitor cells and circulating endothelial cells after acute myocardial infarction or atherothrombotic stroke, and to determine the relationship between these cell counts and plasma concentrations of vascular cell adhesion molecule (VCAM-1) and Von Willebrand factor (VWF) as surrogate markers of endothelial damage and inflammation. In addition, we assessed whether endothelial progenitor cells behave like functional endothelial cells. We included 150 patients with acute myocardial infarction or atherothrombotic stroke and 145 controls. Endothelial progenitor cells [CD45-, CD34+, KDR+, CD133+], circulating endothelial cells [CD45-, CD146+, CD31+], VWF, and VCAM-1 levels were measured in controls (baseline only) and in patients within 24h (baseline) and at 7, 30, and 180 days after the event. Myocardial infarction patients had higher counts of endothelial progenitor cells and circulating endothelial cells than the controls (201.0/mL vs. 57.0/mL; p

Extracellular histones are mediators of inflammation, tissue injury and organ dysfunction. Interactions between circulating histones and vascular endothelial cells are key events in histone‐mediated pathologies. Our aim was to investigate the implication of extracellular histones in the production of the major vasoactive compounds released by human endothelial cells (HUVECs), prostanoids and nitric oxide (NO). HUVEC exposed to increasing concentrations of histones (0.001 to 100 μg/ml) for 4 hrs induced prostacyclin (PGI2) production in a dose‐dependent manner and decreased thromboxane A2 (TXA2) release at 100 μg/ml. Extracellular histones raised cyclooxygenase‐2 (COX‐2) and prostacyclin synthase (PGIS) mRNA and protein expression, decreased COX‐1 mRNA levels and did not change thromboxane A2 synthase (TXAS) expression. Moreover, extracellular histones decreased both, eNOS expression and NO production in HUVEC. The impaired NO production was related to COX‐2 activity and superoxide production since was reversed after celecoxib (10 μmol/l) and tempol (100 μmol/l) treatments, respectively. In conclusion, our findings suggest that extracellular histones stimulate the release of endothelial‐dependent mediators through an up‐regulation in COX‐2‐PGIS‐PGI2 pathway which involves a COX‐2‐dependent superoxide production that decreases the activity of eNOS and the NO production. These effects may contribute to the endothelial cell dysfunction observed in histone‐mediated pathologies.

The Mas receptor is involved in the angiotensin (Ang)-(1-7) vasodilatory actions by increasing nitric oxide production (NO). We have previously demonstrated an increased production of Ang-(1-7) in human umbilical vein endothelial cells (HUVEC) exposed to estradiol (E2), suggesting a potential cross-talk between E2 and the Ang-(1-7)/Mas receptor axis. Here, we explored whether the vasoactive response and NO-related signalling exerted by E2 are influenced by Mas. HUVEC were exposed to 10nM E2 for 24h in the presence or absence of the selective Mas receptor antagonist A779, and the estrogen receptor (ER) antagonist ICI182780 (ICI). E2 increased Akt and endothelial nitric oxide synthase (eNOS) mRNA and protein expression, measured by RT-PCR and Western blot, respectively. Furthermore, E2 increased Akt activity (determined by the levels of phospho-Ser473) and eNOS activity (by the enhanced phosphorylation of Ser1177, the activated form), resulting in increased NO production, which was measured by the fluorescence probe DAF-2-FM. These signalling events were dependent on ER and Mas receptor activation, since they were abolished in the presence of ICI or A779. In ex-vivo functional experiments performed with a small-vessel myograph in isolated mesenteric vessels from wild-type mice pre-contracted with noradrenaline, the relaxant response to physiological concentrations of E2 was blocked by ICI and A779, to the same extent to that obtained in the vessels isolated from Mas-deficient. In conclusion, E2 induces NO production and vasodilation through mechanisms that require Mas receptor activation.

This study investigates the effects of aging and/or ovariectomy on vascular reactivity to thromboxane A2 (TXA2) receptor stimulation with U46619, and the modulation by nitric oxide (NO) and cyclooxygenase (COX) in aorta from female senescence-accelerated mice (SAMP8) and from senescence resistant mice (SAMR1). Five-month-old female SAMR1 and SAMP8 were divided into three groups: sham-operated, ovariectomized and ovariectomized plus estradiol. Twenty-eight days after surgery, thoracic aortic rings were mounted for isometric recording of tension and concentration-response curves for U46619 (10(-10)-3 × 10(-7) M) were performed in the absence and in the presence of the NO synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME, 10(-4) M) and/or COX inhibitor indomethacin (10(-5)M). Vascular superoxide production was detected by dihydroethidium staining on sections of thoracic aorta. NO bioavailability in response to U46619 was suppressed by estrogen withdrawn in young and senescent mice and was restored by the administration of estradiol. In the presence of indomethacin, contractions to U46619 decreased in all groups indicating an aging- and estrogen-dependent modulation of contractile prostanoids. The simultaneous incubation of L-NAME and indomethacin did not change the maximal responses and sensitivities to TXA2 in any group in comparison with untreated aortic segments. The superoxide generation induced by TXA2 was greater in aorta from SAMP8 than in SAMR1. Moreover, in ovariectomized groups superoxide production was further increased and treatment with 17β-estradiol reverted the effects of the ovariectomy. Inhibition of COX with indomethacin prevented the U46619-induced increase in superoxide formation. Our results indicate that NO bioavailability in response to TP receptor activation is both estrogen- and aging-dependent. TXA2 induced contractions are partially mediated by COX activation. Both aging and ovariectomy enhanced COX-dependent component of the TXA2-induced contraction. It is noteworthy that in the absence of estrogen, COX inhibition induces an increase of NO bioavailability. Therefore, in senescent female mice with an experimental menopause, TP-receptor stimulation is responsible for COX activation and enhanced superoxide generation, which may result in reduced NO bioavailability. These effects were reversed by estrogen administration.

Oxidized low density lipoproteins (oxLDLs) act as an etiological factor in the development of atherosclerosis by modifying the biological properties of endothelial cells through mechanisms of vascular inflammation. To deepen the oxLDL changes at cellular level, a transcriptomic analysis of human umbilical artery endothelial cells (HUAECs) treated with oxLDL was performed to identify the modified signaling pathways. Total RNA was isolated from HUAECs treated with oxLDL (100 μg/ml). Gene expression analysis was carried out using Affymetrix oligonucleotide microarrays. Biological pathway analysis was performed using Ingenuity Pathway Analysis software. Microarray assay demonstrated that oxLDL strongly affected two metabolic and signaling transduction pathways: the biosynthesis of steroids, via modification of nine genes that act sequentially in this metabolic pathway, and the Jak-Stat signaling pathway acting through STAT1 and STAT2. By means of qPCR, immunoblot, RNA interference and inhibitors we demonstrate that the mechanism used by oxLDL to activate Jak-Stat signaling pathway in artery endothelial cells is mainly mediated by STAT1. These findings provide a new mechanistic framework to better understand the effects that oxLDLs exert in artery endothelial cell gene expression and provide a source of hypothesis to understand the involvement of oxLDL in diseases in which endothelial cells play a key role, such as atherosclerosis.

INTRODUCTION: The aim of this study was to determine prognostic factors for the risk of new vascular events during the first 6 months after acute myocardial infarction (AMI) or atherothrombotic stroke (AS). We were interested in the prognostic role of endothelial progenitor cells (EPC) and circulating endothelial cells (CEC). METHODS: Between February 2009 and July 2012, 100 AMI and 50 AS patients were consecutively studied in three Spanish centres. Patients with previously documented coronary artery disease or ischemic strokes were excluded. Samples were collected within 24h of onset of symptoms. EPC and CEC were studied using flow cytometry and categorized by quartiles. Patients were followed for up to 6 months. NVE was defined as new acute coronary syndrome, transient ischemic attack (TIA), stroke, or any hospitalization or death from cardiovascular causes. The variables included in the analysis included: vascular risk factors, carotid intima-media thickness (IMT), atherosclerotic burden and basal EPC and CEC count. Multivariate survival analysis was performed using Cox regression analysis. RESULTS: During follow-up, 19 patients (12.66%) had a new vascular event (5 strokes; 3 TIAs; 4 AMI; 6 hospitalizations; 1 death). Vascular events were associated with age (P = 0.039), carotid IMT≥0.9 (P = 0.044), and EPC count (P = 0.041) in the univariate analysis. Multivariate Cox regression analysis showed an independent association with EPC in the lowest quartile (HR: 10.33, 95%CI (1.22-87.34), P = 0.032] and IMT≥0.9 [HR: 4.12, 95%CI (1.21-13.95), P = 0.023]. CONCLUSIONS: Basal EPC and IMT≥0.9 can predict future vascular events in patients with AMI and AS, but CEC count does not affect cardiovascular risk This study was supported in part bySpain’s Ministry of Health (Ministerio de Sanidad y Consumo, FONDO DE INVESTIGACIÓN SANITARIA, Instituto de Salud Carlos III. Grant number: PI080459, RED DE INVESTIGACIÓN/nCARDIOVASCULAR (RIC RD12/0042/0010, RIC RD12/0042/0052, RD12/0042/0020).

Floods and landslides are the natural hazards that most affect Northern Portugal. This paper presents the DISASTER database results for Northern Portugal, containing occurrences of floods and landslides between 1865 and 2010. The research carried out was based on press articles published in national and regional newspapers, but focusing exclusively the occurrences that caused personal damage, including deaths, injured, missing, evacuees and displaced people, regardless of the number of people affected and the economic value of damages. A total of 613 occurrences were recorded, which 18% are landslides and 82% are floods. These occurrences were responsible for 198 deaths, 58 injured, 34 disappeared, 1804 evacuated and 15,918 displaced. The trend analysis shows an increase of 0.17 occurrences/decade. The obtained results show the occurrences concentration in the more urbanized areas and along larger rivers.