Herein we summarize the current knowledge on the bicuspid aortic valve (BAV)-associated aortopathy regarding clinical presentation and disease sub-classification, genetic background, hemodynamics, ...histopathology, cells and signaling, animal models, and biomarkers. Despite enormous efforts in research in all of the above areas, important issues remain unknown: (i) what is the ontogenetic basis of BAV development? (ii) how can we explain the diversity of BAV and associated aortopathy phenotypes? (iii) what are the signaling processes in aortopathy pathogenesis and how can we interfere with these processes? Despite undoubtedly great progress that has been made in the understanding of BAV-associated aortopathy, so far researchers have put together a heap of Lego bricks, but at present it is unclear if the bricks are compatible, how they fit together, and which parts are missing to build the true model of the BAV aorta. A joint approach is needed to accelerate research progress.
The present study was conducted to provide toxicological data on e-cigarette vapours of different e-cigarette brands and liquids from systems viewed as leaders in the e-cigarette market and to ...compare e-cigarette vapour toxicity to the toxicity of conventional strong high-nicotine cigarette smoke. Using an adapted version of a previously constructed cigarette smoke constituent sampling device, we collected the hydrophilic fraction of e-cigarette vapour and exposed human umbilical vein endothelial cells (HUVECs) to the mixture of compounds present in the vapour of 4 different single-use e-cigarettes, 6 different liquid vapours produced by the same refillable e-cigarette, and one e-cigarette with an exchangeable liquid cartridge. After incubation of cells with various concentrations and for various periods of time we analysed cell death induction, proliferation rates, the occurrence of intra-cellular reactive oxygen species, cell morphology, and we also measured e-cigarette heating coil temperatures. Overall, conventional cigarette smoke extract showed the most severe impact on endothelial cells. However, some e-cigarette vapour extracts showed high cytotoxicity, inhibition of cell proliferation, and alterations in cell morphology, which were comparable to conventional high-nicotine cigarettes. The vapours generated from different liquids using the same e-cigarette show substantial differences, pointing to the liquids as an important source for toxicity. E-cigarette vapour-mediated induction of oxidative stress was significant in one out of the 11 analysed vapours. There is a high variability in the acute cytotoxicity of e-cigarette vapours depending on the liquid and on the e-cigarettes used. Some products showed toxic effects close to a conventional high-nicotine cigarette. Liquid nicotine, menthol content, and the formation of acute intracellular reactive oxygen species do not seem to be the central elements in e-cigarette vapour toxicity.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Smoking represents one of the most important preventable risk factors for the development of atherosclerosis. The present review aims at providing a comprehensive summary of published data from ...clinical and animal studies, as well as results of basic research on the proatherogenic effect of smoking. Extensive search and review of literature revealed a vast amount of data on the influence of cigarette smoke and its constituents on early atherogenesis, particularly on endothelial cells. Vascular dysfunction induced by smoking is initiated by reduced nitric oxide (NO) bioavailability and further by the increased expression of adhesion molecules and subsequent endothelial dysfunction. Smoking-induced increased adherence of platelets and macrophages provokes the development of a procoagulant and inflammatory environment. After transendothelial migration and activation, macrophages take up oxidized lipoproteins arising from oxidative modifications and transdifferentiate into foam cells. In addition to direct physical damage to endothelial cells, smoking induces tissue remodeling, and prothrombotic processes together with activation of systemic inflammatory signals, all of which contribute to atherogenic vessel wall changes. There are still great gaps in our knowledge about the effects of smoking on cardiovascular disease. However, we know that smoking cessation is the most effective measure for reversing damage that has already occurred and preventing fatal cardiovascular outcomes.
The demand for decellularized xenogeneic tissues used in reconstructive heart surgery has increased over the last decades. Complete decellularization of longer and tubular aortic sections suitable ...for clinical application has not been achieved so far. The present study aims at analyzing the effect of pressure application on decellularization efficacy of porcine aortas using a device specifically designed for this purpose. Fresh porcine descending aortas of 8 cm length were decellularized using detergents. To increase decellularization efficacy, detergent treatment was combined with pressure application and different treatment schemes. Quantification of penetration depth as well as histological staining, scanning electron microscopy, and tensile strength tests were used to evaluate tissue structure. In general, application of pressure to aortic tissue does neither increase the decellularization success nor the penetration depth of detergents. However, it is of importance from which side of the aorta the pressure is applied. Application of intermittent pressure from the adventitial side does significantly increase the decellularization degree at the intimal side (compared to the reference group), but had no influence on the penetration depth of SDC/SDS at both sides. Although the present setup does not significantly improve the decellularization success of aortas, it is interesting that the application of pressure from the adventitial side leads to improved decellularization of the intimal side. As no adverse effects on tissue structure nor on mechanical properties were observed, optimization of the present protocol may potentially lead to complete decellularization of larger aortic segments.
Graphical Abstract
Pathogenic mechanisms in degenerative thoracic aortic aneurysms (TAA) are still unclear. There is an ongoing debate about whether TAAs are caused by uniform or distinct processes, which would ...obviously have a major impact on future treatment strategies. Clearly, the ultimate outcome of TAA subgroups associated with a tricuspid aortic valve (TAV) or a bicuspid aortic valve (BAV) is the same, namely a TAA. Based on results from our own and others' studies, we decided to compare the different TAAs (TAV and BAV) and controls using a broad array of analyses, i.e., metabolomic analyses, gene expression profiling, protein expression analyses, histological characterization, and matrix-assisted laser desorption ionization imaging. Central findings of the present study are the presence of noncanonical atherosclerosis, pathological accumulation of macrophages, and disturbances of lipid metabolism in the aortic media. Moreover, we have also found that lipid metabolism is impaired systemically. Importantly, all of the above-described phenotypes are characteristic for TAV-TAA only, and not for BAV-TAA. In summary, our results suggest different modes of pathogenesis in TAV- and BAV-associated aneurysms. Intimal atherosclerotic changes play a more central role in TAV-TAA formation than previously thought, particularly as the observed alterations do not follow classical patterns. Atherosclerotic alterations are not limited to the intima but also affect and alter the TAV-TAA media. Further studies are needed to i) clarify patho-relevant intima-media interconnections, ii) define the origin of the systemic alteration of lipid metabolism, and iii) to define valid biomarkers for early diagnosis, disease progression, and successful treatments in TAV-TAAs.
Essential trace elements play an important role in human physiology and are associated with various functions regulating cellular metabolism. Non-essential trace elements, on the other hand, often ...have well-documented toxicities that are dangerous for the initiation and development of diseases due to their widespread occurrence in the environment and their accumulation in living organisms. Non-essential trace elements are therefore regarded as serious environmental hazards that are harmful to health even in low concentrations. Many representatives of these elements are present as pollutants in our environment, and many people may be exposed to significant amounts of these substances over the course of their lives. Among the most common non-essential trace elements are heavy metals, which are also associated with acute poisoning in humans. When these elements accumulate in the body over years of chronic exposure, they often cause severe health damage in a variety of tissues and organs. In this review article, the role of selected essential and non-essential trace elements and their role in the development of exemplary pathophysiological processes in the cardiovascular system will be examined in more detail.
OBJECTIVES—Although cadmium (Cd) is an important and common environmental pollutant and has been linked to cardiovascular diseases, little is known about its effects in initial stages of ...atherosclerosis.
METHODS AND RESULTS—In the 195 young healthy women of the Atherosclerosis Risk Factors in Female Youngsters (ARFY) study, cadmium (Cd) level was independently associated with early atherosclerotic vessel wall thickening (intima-media thickness exceeding the 90th percentile of the distribution; multivariable OR 1.61.1.–2.3, P=0.016). In line, Cd-fed ApoE knockout mice yielded a significantly increased aortic plaque surface compared to controls (9.5 versus 26.0 mm, P<0.004). In vitro results indicate that physiological doses of Cd increase vascular endothelial permeability up to 6-fold by (1) inhibition of endothelial cell proliferation, and (2) induction of a caspase-independent but Bcl-xL-inhibitable form of cell death more than 72 hours after Cd addition. Both phenomena are preceded by Cd-induced DNA strand breaks and a cellular DNA damage response. Zinc showed a potent protective effect against deleterious effects of Cd both in the in vitro and human studies.
CONCLUSION—Our research suggests Cd has promoting effects on early human and murine atherosclerosis, which were partly offset by high Zn concentrations.
Telomere Biology and Thoracic Aortic Aneurysm Aschacher, Thomas; Salameh, Olivia; Enzmann, Florian ...
International journal of molecular sciences,
12/2017, Letnik:
19, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Ascending aortic aneurysms are mostly asymptomatic and present a great risk of aortic dissection or perforation. Consequently, ascending aortic aneurysms are a source of lethality with increased age. ...Biological aging results in progressive attrition of telomeres, which are the repetitive DNA sequences at the end of chromosomes. These telomeres play an important role in protection of genomic DNA from end-to-end fusions. Telomere maintenance and telomere attrition-associated senescence of endothelial and smooth muscle cells have been indicated to be part of the pathogenesis of degenerative vascular diseases. This systematic review provides an overview of telomeres, telomere-associated proteins and telomerase to the formation and progression of aneurysms of the thoracic ascending aorta. A better understanding of telomere regulation in the vascular pathology might provide new therapeutic approaches. Measurements of telomere length and telomerase activity could be potential prognostic biomarkers for increased risk of death in elderly patients suffering from an aortic aneurysm.
Pathological impairment of elastic fiber and other extracellular matrix (ECM) components are described for the aortic media of ascending thoracic aortic aneurysms (aTAA) but the exact pathological ...impairment of the structure and its degree still needs further investigations. To evaluate the quantity and quality of elastic fiber sheets and other ECM structures (e.g. collagen), cells were removed from different types of aneurysmal tissues (tricuspid aortic valve TAV associated-, bicuspid aortic valve BAV associated-aneurysmal tissue and acute aortic dissections AAD) using 2.5% sodium hydroxide (NaOH) and compared to decellularized control aortic tissue. Likewise, native tissue has been analysed. To evaluate the 2D- (histological evaluation, fluorescence- and auto-fluorescence based staining methods) and the 3D structure (scanning electron microscopic SEM examination) of the medial layer we first analysed for a successful decellularization. After proving for successful decellularization, we quantified the amount of elastic fiber sheets, elastin and other ECM components including collagen. Aside from clearly visible focal elastic fiber loss in TAV-aTAA tissue, decellularization resulted in reduction of elastic fiber auto-fluorescence properties, which is perhaps an indication from a disease-related qualitative impairment of elastic fibers, visible only after contact with the alkaline solution. Likewise, the loss of collagen amount in BAV-aTAA and TAV-aTAA tissue (compared to non-decellularized tissue) after contact with NaOH indicates a prior disease-associated impairment of collagen. Although the amount of ECM was not changed in type A dissection tissue, detailed electron microscopic evaluation revealed changes in ECM quality, which worsened after contact with alkaline solution but were not visible after histological analyses. Apart from the improved observation of the samples using electron microscopy, contact of aneurysmal and dissected tissue with the alkaline decellularization solution revealed potential disease related changes in ECM quality which can partly be connected to already published data, but have to be proven by further studies.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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