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Le Goff M.M.,University of Manchester | Sutton M.J.,University of Manchester | Slevins M.,Manchester Metropolitan University | Slevins M.,Institute Catala Of Ciencies Cardiovasculars | And 3 more authors.
Journal of Biological Chemistry | Year: 2012

Opticin is an extracellular matrix glycoprotein that we identified associated with the collagen network of the vitreous humor of the eye. Recently, we discovered that opticin possesses anti-angiogenic activity using a murine oxygen-induced retinopathy model: here, we investigate the underlying mechanism. Using an ex vivo chick chorioallantoic membrane assay, we show that opticin inhibits angiogenesis when stimulated by a range of growth factors. We show that it suppresses capillary morphogenesis, inhibits endothelial invasion, and promotes capillary network regression in three-dimensional matrices of collagen and Matrigel™. We then show that opticin binds to collagen and thereby competitively inhibits endothelial cell interactions with collagen via α 1β 1 and α 2β 1 integrins, thereby preventing the strong adhesion that is required for proangiogenic signaling via these integrins. © 2012 by The American Society for Biochemistry and Molecular Biology, Inc. Source

Bayes De Luna A.,Institute Catala Of Ciencies Cardiovasculars | Elosua R.,CIBER ISCIII
Revista Espanola de Cardiologia | Year: 2012

Sudden death is probably the greatest challenge in modern cardiology. After reviewing its history, we describe the epidemiology of sudden death and its associated diseases. We highlight its physiopathologic aspects, including the factors that act on vulnerable myocardium triggering the final arrhythmia, mainly ventricular fibrillation and, to a lesser extent, bradycardia and sudden death. We emphasize the relevance of acute ischemia, ventricular dysfunction and genetic factors, not only in genetic heart disease, but also as triggers of sudden death in acute and chronic ischemic heart disease. Finally, we describe the best way to identify candidates at risk, discuss how to prevent sudden death, and outline the best approach to managing a patient resuscitated from cardiac arrest. © 2012 Sociedad Española de Cardiolog?́a. Published by Elsevier España, S.L. All rights reserved. Source

Fiol M.,Hospital Son Espases | Carrillo A.,Hospital Son Espases | Rodriguez A.,Hospital Son Espases | Pascual M.,Hospital Son Espases | And 2 more authors.
Journal of Electrocardiology | Year: 2012

Acute coronary syndromes due to involvement of the left main trunk usually present with subtotal occlusion and electrocardiographic pattern with predominant ST depression (non-ST-elevation myocardial infarction). The cases with complete occlusion frequently present an ST-elevation myocardial infarction pattern, but these patients usually die before reaching the hospital. We present a series of 7 patients with total left main trunk occlusion without collateral circulation showing ST-elevation myocardial infarction pattern. The electrocardiographic pattern is similar to left anterior descending coronary artery proximal occlusion to first septal and first diagonal but without ST elevation in V1 and aVR because of left circumflex coronary artery compromise. In 4 (60%) of 7 of cases, there is also advanced right bundle-branch block plus superoanterior hemiblock. Despite severe clinical state at entrance (5/7 presented cardiac arrest/cardiogenic shock), 3 patients (43%) survived after percutaneous coronary intervention. © 2012 Elsevier Inc. All rights reserved. Source

Indolfi C.,University of Catanzaro | Rodriguez C.,Institute Catala Of Ciencies Cardiovasculars | Rodriguez-Calvo R.,Institute Catala Of Ciencies Cardiovasculars | Bauriedel G.,University of Bonn | And 4 more authors.
Arteriosclerosis, Thrombosis, and Vascular Biology | Year: 2013

OBJECTIVE - : Atherosclerosis and restenosis are multifactorial diseases associated with abnormal vascular smooth muscle cell (VSMC) proliferation. Nuclear factor-Y (NF-Y) plays a major role in transcriptional activation of the CYCLIN B1 gene (CCNB1), a key positive regulator of cell proliferation and neointimal thickening. Here, we investigated the role of NF-Y in occlusive vascular disease. APPROACH AND RESULTS - : We performed molecular and expression studies in cultured cells, animal models, and human tissues. We find upregulation of NF-Y and cyclin B1 expression in proliferative regions of murine atherosclerotic plaques and mechanically induced lesions, which correlates with higher binding of NF-Y to target sequences in the CCNB1 promoter. NF-YA expression in neointimal lesions is detected in VSMCs, macrophages, and endothelial cells. Platelet-derived growth factor-BB, a main inductor of VSMC growth and neointima development, induces the recruitment of NF-Y to the CCNB1 promoter and augments both CCNB1 mRNA expression and cell proliferation through extracellular signal-regulated kinase 1/2 and Akt activation in rat and human VSMCs. Moreover, adenovirus-mediated overexpression of a NF-YA-dominant negative mutant inhibits platelet-derived growth factor-BB-induced CCNB1 expression and VSMC proliferation in vitro and neointimal lesion formation in a mouse model of femoral artery injury. We also detect NF-Y expression and DNA-binding activity in human neointimal lesions. CONCLUSIONS - : Our results identify NF-Y as a key downstream effector of the platelet-derived growth factor-BB-dependent mitogenic pathway that is activated in experimental and human vasculoproliferative diseases. They also identify NF-Y inhibition as a novel and attractive strategy for the local treatment of neointimal formation induced by vessel denudation. © 2013 American Heart Association, Inc. Source

Monasterio V.,CIBER ISCIII | Monasterio V.,Aragon Institute of Engineering Research | Laguna P.,CIBER ISCIII | Laguna P.,Aragon Institute of Engineering Research | And 7 more authors.
Heart Rhythm | Year: 2012

Background: T-wave alternans (TWA) is a well-documented noninvasive electrocardiographic (ECG) method useful for identifying patients at risk for sudden cardiac death (SCD). Objective: The purpose of this study was to evaluate whether the long-term average TWA activity on Holter monitoring provides prognostic information in patients with chronic heart failure. Methods: Twenty-four-hour Holter ECGs from 650 ambulatory patients with mild-to-moderate chronic heart failure were analyzed in the study. Average TWA activity was measured by using a fully automated multilead technique, and 2 indices were proposed to quantify TWA: an index quantifying the average TWA activity in the whole recording (IAA), which was used to define a positive/negative TWA test, and an index quantifying the average TWA activity at heart rates between 80 and 90 beats/min (IAA90). Results: Patients were divided into TWA positive (TWA+) and TWA negative (TWA) groups by setting a cut point of 3.7 μV for IAA, corresponding to the 75th percentile of the distribution of IAA in the population. After a median follow-up of 48 months, the survival rate was significantly higher in the TWA group for cardiac death and SCD (p =.017 and p =.001, respectively). Multivariate Cox proportional hazards analysis revealed that both TWA+ and IAA90 were associated with SCD with hazard rates of 2.29 (p =.004) and 1.07 per μV (p =.046), respectively. Conclusion: The average TWA activity measured automatically from Holter ECGs predicted SCD in patients with mild-to-moderate chronic heart failure. © 2012 Heart Rhythm Society. All rights reserved. Source

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