1,720,964 research outputs found
Effetto dell’ivabradina nelle fasi iniziali e nella progressione dell’aterosclerosi
No full textEffect of ivabradine in the initial steps and in the progression of the atherosclerosis Purpose: Ivabradine reduces heart rate (HR) by selectively inhibiting the If current in the sinus node.
A sub-group of the BEAUTifUL study showed that ivabradine reduces the incidence of myocardial infarction in coronary artery disease (CAD) patients with HR ≥ 70bpm, suggesting a protective effect on the arterial wall. The SIGNifY study is currently testing this hypothesis in more than 19000 CAD patients. In dyslipidaemic mice, ivabradine improves vascular function and reduces aortic plaques area. It has been suggested that ivabradine may exert a protective activity by decreasing low/oscillatory shear stress, which is proinflammatory in the endothelium.
This study aims to determine if HR reduction with ivabradine induces an atheroprotective gene expression profile in the endothelium of dyslipidaemic mice before plaque formation. Methods: 6 week-old ApoE deficient mice (n=6), fed a chow diet, were treated with ivabradine (30 mg/Kg/day, in drinking water) for 2 or 4 weeks. Two control groups (n=6) received no ivabradine. Ivabradine reduced HR by 17.4% and 22.9% in mice treated for 2 weeks and 4 weeks respectively. At the end of treatment, endothelium-enriched RNA was isolated from the aortic arch. Gene expression was analyzed by Agilent Whole Mouse Gene Expression Microarray (60k probes). Pathway analysis was performed using DAVID tools. Principal components analysis showed that most of the variability in gene expression can be attributed to ivabradine treatment and was independent of treatment duration. Differentially expressed genes were selected as having a ≥ 1.5-fold expression difference between treated and untreated groups with a p-value ≤ 0.01 at unpaired t-test. Results: Treatment induced changes in the expression of 930 transcripts. Shear stress-modulated pathways such as MAPK signalling and steroid biosynthesis process (both inhibited by treatment) were among the most significantly affected pathways (p-value = 0.0065 and 0.0009, respectively). We found up-regulation of anti-inflammatory genes and down-regulation of pro-apoptotic and pro-inflammatory genes, the majority of which were NF-kappa B and/or Ang II-regulated genes. Among them, the receptor for oxidized lipoprotein (Olr1) was strongly downregulated (3.2 fold).
Conclusions: In dyslipidaemic mice, short term treatment with ivabradine induces an atheroprotective gene expression profile in the endothelium. Since many of the affected genes are shear stress regulated, our data suggest that shear stress frequency modulation could be part of the molecular mechanisms by which ivabradine protects the endothelium
Angiopoietin-like proteins as therapeutic targets for cardiovascular disease: focus on lipid disorders
No full textIntroduction: Angiopoietin-like (ANGPTL) proteins belong to a family of eight secreted factors that are structurally related to proteins that modulate angiogenesis; these are commonly known as angiopoietins. Angiopoietin-like proteins, ANGPTL3, ANGPTL4, and ANGPTL8 (the "ANGPT L3-4-8 triad"), have surfaced as principal regulators of plasma lipid metabolism by functioning as potent inhibitors of lipoprotein lipase. The targeting of these proteins may open up future therapeutic avenues for metabolic and cardiovascular disease.Areas covered: This article systematically summarizes the compelling literature that describes the mechanistic roles of ANGPTL3, 4, and 8 in lipid metabolism; this emphasizes their importance in determining the risk of cardiovascular disease. We shed light on population-based studies linking loss-of-function variations in ANGPTL3, 4, and 8 with decreased risk of metabolic conditions and cardiovascular disorders. We also discuss how the targeting of the ANGPT L3-4-8 triad could one day offer therapeutic benefit.Expert opinion: Monoclonal antibodies and antisense oligonucleotides that target ANGPTL3, 4, and 8 are potentially an efficient therapeutic strategy for hypertriglyceridemia and cardiovascular risk reduction, especially in patients with limited treatment options. These innovative therapeutical approaches are at an embryonic stage in development and hence further investigations are necessary for eventual use in humans
The role of Notch pathway in cardiovascular diseases
No full textThe recent increase in human lifespan, coupled with unhealthy diets and lifestyles have led to an unprecedented increase in cardiovascular diseases. Even in the presence of a wide range of therapeutic options with variable efficacy, mortality due to heart failure is still high and there is a need to identify new therapeutic targets. Genetic and in vitro studies have implicated the Notch signalling in the development and maintenance of the cardiovascular system through a direct effect on biological functions of vascular cells (endothelial and vascular smooth muscle cells) and cardiomyocytes. Notch signalling is also involved in the modulation of inflammation, which plays a major role in causing and exacerbating cardiovascular diseases. The Notch pathway could represent a new therapeutic target for the treatment of cardiovascular diseases
Cardiomyocyte-derived exosomal microRNA-92a mediates post-ischemic myofibroblast activation both in vitro and ex vivo.
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Cardiotoxicity of Anticancer Drugs: Molecular Mechanisms and Strategies for Cardioprotection
Full text linkChemotherapy and targeted therapies have significantly improved the prognosis of oncology patients. However, these antineoplastic treatments may also induce adverse cardiovascular effects, which may lead to acute or delayed onset of cardiac dysfunction. These common cardiovascular complications, commonly referred to as cardiotoxicity, not only may require the modification, suspension, or withdrawal of life-saving antineoplastic therapies, with the risk of reducing their efficacy, but can also strongly impact the quality of life and overall survival, regardless of the oncological prognosis. The onset of cardiotoxicity may depend on the class, dose, route, and duration of administration of anticancer drugs, as well as on individual risk factors. Importantly, the cardiotoxic side effects may be reversible, if cardiac function is restored upon discontinuation of the therapy, or irreversible, characterized by injury and loss of cardiac muscle cells. Subclinical myocardial dysfunction induced by anticancer therapies may also subsequently evolve in symptomatic congestive heart failure. Hence, there is an urgent need for cardioprotective therapies to reduce the clinical and subclinical cardiotoxicity onset and progression and to limit the acute or chronic manifestation of cardiac damages. In this review, we summarize the knowledge regarding the cellular and molecular mechanisms contributing to the onset of cardiotoxicity associated with common classes of chemotherapy and targeted therapy drugs. Furthermore, we describe and discuss current and potential strategies to cope with the cardiotoxic side effects as well as cardioprotective preventive approaches that may be useful to flank anticancer therapies
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Arginine and Endothelial Function
No full textArginine (L-arginine), is an amino acid involved in a number of biological processes, including the biosynthesis of proteins, host immune response, urea cycle, and nitric oxide production. In this systematic review, we focus on the functional role of arginine in the regulation of endothelial function and vascular tone. Both clinical and preclinical studies are examined, analyzing the effects of arginine supplementation in hypertension, ischemic heart disease, aging, peripheral artery disease, and diabetes mellitus
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
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