Cigarette smoke is an aerosol that contains >4,000 chemicals, including nicotine, carbon monoxide, acrolein, and oxidant compounds. Exposure to cigarette smoke induces multiple pathological effects ...in the endothelium, several of which are the result of oxidative stress initiated by reactive oxygen species, reactive nitrogen species, and other oxidant constituents of cigarette smoke. Cigarette-smoke exposure interferes adversely with the control of all stages of plaque formation and development and pathological thrombus formation. The reactive oxygen species in cigarette smoke contribute to oxidative stress, upregulation of inflammatory cytokines, and endothelial dysfunction, by reducing the bioavailability of nitric oxide. Plaque formation and the development of vulnerable plaques also result from exposure to cigarette smoke via the enhancement of inflammatory processes and the activation of matrix metalloproteases. Moreover, exposure to cigarette smoke results in platelet activation, stimulation of the coagulation cascade, and impairment of anticoagulative fibrinolysis. Many cigarette-smoke-mediated prothrombotic changes are quickly reversible upon smoking cessation. Public health efforts should urgently promote our understanding of current cigarette-smoke-induced cardiovascular pathology to encourage individuals to reduce their exposure to cigarette smoke and, therefore, the detrimental consequences of associated atherothrombotic disease.
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.
High-quality matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) of lipids in biological tissue relies on the fabrication of a homogeneous matrix coating featuring best ...possible analyte integration. This communication addresses a matrix vapor deposition/recrystallization process for the application of 1,5-diaminonaphthalene (1,5-DAN) onto slices of human aortic tissue. The matrix coating is compatible with both positive- as well as negative-ion-mode MALDI MSI facilitating a significantly enhanced detection of lipid-related signals in different cell layers of blood vessel walls.
Graphical abstract
Thoracic aortic dissections (TAD) are life-threatening events mostly requiring immediate surgical treatment. Although dissections mainly occur independently of thoracic aortic aneurysms (TAA), both ...share a high comorbidity. There are several indications for an involvement of the immune system in the development of TAD, just as in TAA. Nevertheless, specific disease-relevant genes, biomolecular processes, and immune-specific phenotypes remain unknown.
RNA from isolated aortic smooth muscle cells from TAD (n = 4), TAA (n = 3), and control patients were analyzed using microarray-based technologies. Additionally, three publicly available bulk RNA-seq studies of TAD (n = 23) and controls (n = 17) and one single-cell RNA-seq study of TAA (n = 8) and controls (n = 3) were analyzed. Differentially expressed genes were identified and used to identify affected pathways in TAD. Five selected genes were validated by quantitative real-time polymerase chain reaction (PCR).
We identified 37 genes that were significantly dysregulated in at least three TAD studies-24 of them were not shown to be associated with TAD, yet. Gene ontology analysis showed that immune response was significantly affected. Five of the genes (
,
,
,
, and
) were revealed as core genes that affect immune response in TAD. We compared the gene expression of those genes to TAA and found that
,
and potentially also
were upregulated in TAD.
The identified immune-related genes showed TAD-specificity, independent of possible pre-existing comorbidities like TAA. So, these genes represent potential biomarkers and therapeutic targets linked to the immune response in acute TAD. Additionally, we identified a set of differentially expressed genes that represents a resource for further studies.
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.
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.
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.
Oceanic Anoxic Event 2 (OAE 2) (∼ 93.5 Ma) is characterized by widespread marine anoxia and elevated burial rates of organic matter. However, the factors that led to this widespread marine ...deoxygenation and the possible link with climatic change remain debated. Here, we report long-term biomarker records of water-column anoxia, water-column and photic zone euxinia (PZE), and sea surface temperature (SST) from Demerara Rise in the equatorial Atlantic that span 3.8 Myr of the late Cenomanian to Turonian, including OAE 2. We find that total organic carbon (TOC) content is high but variable (0.41 wt %–17 wt %) across the Cenomanian and increases with time. This long-term TOC increase coincides with a TEX86-derived SST increase from ∼ 35 to 40 ∘C as well as the episodic occurrence of 28,30-dinorhopane (DNH) and lycopane, indicating warming and expansion of the oxygen minimum zone (OMZ) predating OAE 2. Water-column euxinia persisted through much of the late Cenomanian, as indicated by the presence of C35 hopanoid thiophene but only reached the photic zone during OAE 2, as indicated by the presence of isorenieratane. Using these biomarker records, we suggest that water-column anoxia and euxinia in the equatorial Atlantic preceded OAE 2 and this deoxygenation was driven by global warming.
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