1,721,144 research outputs found
INCREASED ENDOPLASMIC RETICULUM STRESS AND NRF2 REPRESSION IN PERIPHERAL BLOOD MONONUCLEAR CELLS OF PATIENTS WITH STABLE CORONARY ARTERY DISEASE
No full textEndoplasmic reticulum (ER) stress is involved in the pathophysiology of atherosclerosis. Insults interfering with endoplasmic reticulum (ER) function, lead to accumulation of unfolded and misfolded proteins in ER that initiates the unfolded protein response (UPR). When the UPR fails to control the level of unfolded and misfolded proteins, ER-initiated apoptotic signaling is induced.
We evaluated: 1) the UPR and ER-initiated apoptotic signaling in peripheral blood mononuclear cells (PBMC) of stable coronary artery disease patients (CAD); 2) PBMC content of oxidation products of phospholipid 1-palmitoyl-2-arachidonyl-sn-glycero-3-phosphorylcholine (oxPAPC); 3) the possible origin of oxPAPC in PBMC; 4) the expression of nuclear erytroid-related factor 2 (Nrf2)/antioxidant related element (ARE), a cellular defence mechanism.
29 CAD and 28 matched controls were enrolled. Expression of glucose-regulated protein 78 kDa (GRP78/BiP) as representative of UPR, and of C/EBP homologous protein (CHOP) as representative of ER-apoptosis, were significantly higher in CAD than in controls (p<0.01). Concentrations of oxPAPC in PBMC, in plasma and in low density lipoprotein (LDL) resulted significantly higher in CAD than in controls (p<0.01). The oxPAPC in PBMC may derive from circulating ox-LDL. Nrf2/ARE gene expression and circulating and cellular glutathione (GSH) were significantly lower in CAD than in controls (p<0.01). In in vitro studies, increasing amounts of oxPAPC induced a dose-dependent increase of CHOP and apoptosis-related protein expression (p<0.01) and a progressive decrease of Nrf2/ARE gene expression (p<0.01).
In PBMC of CAD patients there is an activation of UPR and of ER-initiated apoptotic signaling, possibly related to abnormal concentration of oxPAPC in PBMC
CIGARETTE SMOKING BLOCKS THE PROTECTIVE EXPRESSION OF Nrf2/ARE PATHWAY IN BLOOD CELLS OF YOUNG HEAVY SMOKERS FAVOURING INFLAMMATION: RELATION WITH ENDOTHELIAL FUNCTION AND CAROTID INTIMA MEDIA THICKNESS
No full textBackground: Although oxidative stress plays a major role in endothelial dysfunction (ED), the role of glutathione (GSH), of
nuclear erythroid-related factor 2 (Nrf2) and of related antioxidant genes (ARE) are yet unknown. In this study we combined
an in vivo with an in vitro model to assess whether cigarette smoking affects flow-mediated vasodilation (FMD), GSH
concentrations and the Nrf2/ARE pathway in human umbilical vein endothelial cells (HUVECs).
Methods and Results: 52 healthy subjects (26 non-smokers and 26 heavy smokers) were enrolled in this study. In smokers
we demonstrated increased oxidative stress, i.e., reduced concentrations of GSH and increased concentrations of oxidation
products of the phospholipid 1-palmitoyl-2-arachidonyl-sn-glycero-3-phosphorylcholine (oxPAPC) in serum and in
peripheral blood mononuclear cells (PBMC), used as in vivo surrogates of endothelial cells. Moreover we showed
impairment of FMD in smokers and a positive correlation with the concentration of GSH in PBMC of all subjects. In HUVECs
exposed to smokers’ serum but not to non-smokers’ serum we found that oxidative stress increased, whereas nitric oxide
and GSH concentrations decreased; interestingly the expression of Nrf2, of heme oxygenase-1 (HO-1) and of glutamatecysteine
ligase catalytic (GCLC) subunit, the rate-limiting step of synthesis of GSH, was decreased. To test the hypothesis
that the increased oxidative stress in smokers may have a causal role in the repression of Nrf2/ARE pathway, we exposed
HUVECs to increasing concentrations of oxPAPC and found that at the highest concentration (similar to that found in
smokers’ serum) the expression of Nrf2/ARE pathway was reduced. The knockdown of Nrf2 was associated to a significant
reduction of HO-1 and GCLC expression induced by oxPAPC in ECs.
Conclusions: In young smokers with ED a novel further consequence of increased oxidative stress is a repression of Nrf2/
ARE pathway leading to GSH depletion
Progeria, atherosclerosis and clonal hematopoiesis: links and future perspectives
No full textThe main actors of this review are Hutchinson-Gilford progeria syndrome (HGPS) and atherosclerosis. HGPS is a very rare disease with no definitively approved specific drugs. Atherosclerosis is a very common disease with a more consolidated treatment strategy. Nevertheless, common mechanisms are shared by both these diseases, particularly related to inflammation, oxidative and endoplasmic reticulum (ER) stress. Pathways regulated by Nuclear factor E2 related factor (Nrf2), Nuclear factor kappa B (NF-kB) and related to the Unfolded Protein Response (UPR) and ER stress are receiving increasing attention. In HGPS "not omnia" happen(s) "cum tempore", that means that HGPS patients have atherosclerotic complications before their time. The third actor is clonal hematopoiesis: it constitutes a link between ageing and atherosclerosis. This review aims to analyse the current knowledge of atherosclerosis and clonal hematopoiesis in order to suggest therapeutic strategies to correct the timing of the atherosclerosis progression in HGPS. The goal for HGPS is a shift from "not omnia cum tempore" to "omnia cum tempore" in terms of significant lifespan extension by postponing atherosclerosis-related complications
RECENT ACQUISITIONS ABOUT THE ROLE OF ENDOPLASMIC RETICULUM STRESS AND NRF2 SIGNALLING IN CARDIOVASCULAR DISEASES AND IN ATHEROSCLEROTIC PLAQUE VULNERABILITY
No full textInsults interfering with endoplasmic reticulum (ER) function lead to the accumulation of unfolded and misfolded proteins in the ER. An excess of proteins folding in the ER is known as ER stress. This condition initiates the unfolded protein response (UPR). When the UPR fails to control the level of unfolded and misfolded proteins, ER-initiated apoptotic signalling is induced. This review investigates the role of the inflammatory and oxidative impairment as possible UPR and ER apoptosis inductors in triggering the ER stress response. Moreover, the role of the protective nuclear erythroid-related factor 2 (Nrf2)/antioxidant-related element (ARE) and the activation of the pro-inflammatory nuclear factor-kappa B (NF-kB) are analysed. The Authors summarize evidence that oxidative stress, inflammation and ER stress are closely entwined phenomena. They are involved in the pathogenesis of different settings of cardiovascular diseases.The Authors' own experiences and current literature data are collected, focusing on three precise topics: atherosclerotic plaque, coronary artery disease and diabetes.The current field of research will provide a platform for study and application to several other conditions in which oxidative stress, ER stress and inflammation are key features. Future studies in this area may identify the most promising molecules to be investigated as common targets for cardiovascular diseases.Insults interfering with endoplasmic reticulum (ER) function lead to the accumulation of unfolded and misfolded proteins in the ER. An excess of proteins folding in the ER is known as ER stress. This condition initiates the unfolded protein response (UPR). When the UPR fails to control the level of unfolded and misfolded proteins, ER-initiated apoptotic signalling is induced. This review investigates the role of the inflammatory and oxidative impairment as possible UPR and ER apoptosis inductors in triggering the ER stress response. Moreover, the role of the protective nuclear erythroid-related factor 2 (Nrf2)/antioxidant-related element (ARE) and the activation of the pro-inflammatory nuclear factor-kappa B (NF-kB) are analysed. The Authors summarize evidence that oxidative stress, inflammation and ER stress are closely entwined phenomena. They are involved in the pathogenesis of different settings of cardiovascular diseases.The Authors' own experiences and current literature data are collected, focusing on three precise topics: atherosclerotic plaque, coronary artery disease and diabetes.The current field of research will provide a platform for study and application to several other conditions in which oxidative stress, ER stress and inflammation are key features. Future studies in this area may identify the most promising molecules to be investigated as common targets for cardiovascular diseases
The role of Neutrophil Extracellular Traps in Covid-19: Only an hypothesis or a potential new field of research?
No full textletter to Edito
Unstable Angina: focus on NF-kB, inflammation and possible link to Neutrophil Extracellular Traps
No full text
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
Young smoker “ABCD” vascular assessment: a four-step ultrasound examination for detecting peripheral, extra and intra-cranial early arterial damage
Full text linkCigarette smoking is known as a major risk factor in the pathogenic mechanisms of stroke, coronary and peripheral artery disease (CAD and PAD), even in young subjects. The aim of this study is the creation of a four-step ultrasound examination to evaluate and monitor the peripheral, the extra and the intra-cranial assessment of the arterial early damage in smokers. The evaluations of A, the Ankle-brachial index, ABI, B, the Breath holding index, BHI, C, the Carotid intima media thickness, CIMT, and D, the Diameter of the abdominal aorta represent the "ABCD" assessment
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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