scholarly journals Inflammasomes in the Pathophysiology of Aortic Disease

Cells ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2433
Author(s):  
Markus Wortmann ◽  
Andreas S. Peters ◽  
Philipp Erhart ◽  
Daniel Körfer ◽  
Dittmar Böckler ◽  
...  

Aortic diseases comprise aneurysms, dissections, and several other pathologies. In general, aging is associated with a slow but progressive dilation of the aorta, along with increased stiffness and pulse pressure. The progression of aortic disease is characterized by subclinical development or acute presentation. Recent evidence suggests that inflammation participates causally in different clinical manifestations of aortic diseases. As of yet, diagnostic imaging and surveillance is mainly based on ultrasonography, computed tomography (CT), and magnetic resonance imaging (MRI). Little medical therapy is available so far to prevent or treat the majority of aortic diseases. Endovascular therapy by the introduction of covered stentgrafts provides the main treatment option, although open surgery and implantation of synthetic grafts remain necessary in many situations. Because of the risks associated with surgery, there is a need for identification of pharmaceutical targets interfering with the pathophysiology of aortic remodeling. The participation of innate immunity and inflammasome activation in different cell types is common in aortic diseases. This review will thus focus on inflammasome activities in vascular cells of different chronic and acute aortic diseases and discuss their role in development and progression. We will also identify research gaps and suggest promising therapeutic targets, which may be used for future medical interventions.

2021 ◽  
Vol 12 ◽  
Author(s):  
Tharmarajan Ramprasath ◽  
Young-Min Han ◽  
Donghong Zhang ◽  
Chang-Jiang Yu ◽  
Ming-Hui Zou

Aortic diseases are the primary public health concern. As asymptomatic diseases, abdominal aortic aneurysm (AAA) and atherosclerosis are associated with high morbidity and mortality. The inflammatory process constitutes an essential part of a pathogenic cascade of aortic diseases, including atherosclerosis and aortic aneurysms. Inflammation on various vascular beds, including endothelium, smooth muscle cell proliferation and migration, and inflammatory cell infiltration (monocytes, macrophages, neutrophils, etc.), play critical roles in the initiation and progression of aortic diseases. The tryptophan (Trp) metabolism or kynurenine pathway (KP) is the primary way of degrading Trp in most mammalian cells, disturbed by cytokines under various stress. KP generates several bioactive catabolites, such as kynurenine (Kyn), kynurenic acid (KA), 3-hydroxykynurenine (3-HK), etc. Depends on the cell types, these metabolites can elicit both hyper- and anti-inflammatory effects. Accumulating evidence obtained from various animal disease models indicates that KP contributes to the inflammatory process during the development of vascular disease, notably atherosclerosis and aneurysm development. This review outlines current insights into how perturbed Trp metabolism instigates aortic inflammation and aortic disease phenotypes. We also briefly highlight how targeting Trp metabolic pathways should be considered for treating aortic diseases.


2021 ◽  
Vol 12 ◽  
Author(s):  
Haiyan Ma ◽  
Jasper F. W. Chan ◽  
Yen Pei Tan ◽  
Lin Kui ◽  
Chi-Ching Tsang ◽  
...  

Talaromyce marneffei is an important thermally dimorphic pathogen causing disseminated mycoses in immunocompromised individuals in southeast Asia. Previous studies have suggested that NLRP3 inflammasome plays a critical role in antifungal immunity. However, the mechanism underlying the role of NLRP3 inflammasome activation in host defense against T. marneffei remains unclear. We show that T. marneffei yeasts but not conidia induce potent IL-1β production. The IL-1β response to T. marneffei yeasts is differently regulated in different cell types; T. marneffei yeasts alone are able to induce IL-1β production in human PBMCs and monocytes, whereas LPS priming is essential for IL-1β response to yeasts. We also find that Dectin-1/Syk signaling pathway mediates pro-IL-1β production, and NLRP3-ASC-caspase-1 inflammasome is assembled to trigger the processing of pro-IL-1β into IL-1β. In vivo, mice deficient in NLRP3 or caspase-1 exhibit higher mortality rate and fungal load compared to wild-type mice after systemic T. marneffei infection, which correlates with the diminished recruitment of CD4 T cells into granulomas in knockout mice. Thus, our study first demonstrates that NLRP3 inflammasome contributes to host defense against T. marneffei infection.


2012 ◽  
Vol 74 (4) ◽  
pp. 213-223 ◽  
Author(s):  
Richard A. Stein ◽  
Devra Lee Davis

Epigenetics is emerging as one of the most dynamic and vibrant biomedical areas. Multiple lines of evidence confirm that inherited genetic changes alone cannot fully explain all phenotypic characteristics of live organisms, and additional factors, which are not encoded in the DNA sequence, are involved. The contribution of non-genetic factors is perhaps best illustrated by monozygotic twins, which, despite sharing nearly identical DNA sequences, are often discordant for diseases they develop. Even when twins develop the same condition, they may experience different clinical manifestations or clinical onset at different ages. Epigenetic mechanisms explain how a zygote can differentiate into >220 different cell types that form an adult organism and, with rare exceptions, share the same DNA. Increasingly, epigenetic factors emerge, in addition to genetic ones, as important contributors to carcinogenesis. Epigenetic modifications also explain the biological impact of environmental factors, including chemical and dietary compounds, physical agents, pathogens linked to cancer, and social–emotional interactions. Unlike genetic changes, epigenetic changes are reversible, a characteristic that opens unprecedented therapeutic avenues, exemplified by the first epigenetic drugs that were recently approved. Understanding the combined contribution of genetic and epigenetic factors to gene expression will be essential to dissect the biological networks shaping development and disease, and to develop a new array of prophylactic, diagnostic, and therapeutic applications.


Author(s):  
U. Aebi ◽  
P. Rew ◽  
T.-T. Sun

Various types of intermediate-sized (10-nm) filaments have been found and described in many different cell types during the past few years. Despite the differences in the chemical composition among the different types of filaments, they all yield common structural features: they are usually up to several microns long and have a diameter of 7 to 10 nm; there is evidence that they are made of several 2 to 3.5 nm wide protofilaments which are helically wound around each other; the secondary structure of the polypeptides constituting the filaments is rich in ∞-helix. However a detailed description of their structural organization is lacking to date.


1992 ◽  
Vol 67 (01) ◽  
pp. 154-160 ◽  
Author(s):  
P Meulien ◽  
M Nishino ◽  
C Mazurier ◽  
K Dott ◽  
G Piétu ◽  
...  

SummaryThe cloning of the cDNA encoding von Willebrand factor (vWF) has revealed that it is synthesized as a large precursor (pre-pro-vWF) molecule and it is now clear that the prosequence or vWAgll is responsible for the intracellular multimerization of vWF. We have cloned the complete vWF cDNA and expressed it using a recombinant vaccinia virus as vector. We have characterized the structure and function of the recombinant vWF (rvWF) secreted from five different cell types: baby hamster kidney (BHK), Chinese hamster ovary (CHO), human fibroblasts (143B), mouse fibroblasts (L) and primary embryonic chicken cells. Forty-eight hours after infection, the quantity of vWF antigen found in the cell supernatant varied from 3 to 12 U/dl depending on the cell type. By SDS-agarose gel electrophoresis, the percentage of high molecular weight forms of vWF varied from 39 to 49% relative to normal plasma for BHK, CHO, 143B and chicken cells but was less than 10% for L cells. In all cell types, the two anodic subbands of each multimer were missing. The two cathodic subbands were easily detected only in BHK and L cells. By SDS-PAGE of reduced samples, pro-vWF was present in similar quantity to the fully processed vWF subunit in L cells, present in moderate amounts in BHK and CHO and in very low amounts in 143B and chicken cells. rvWF from all cells bound to collagen and to platelets in the presence of ristocetin, the latter showing a high correlation between binding efficiency and degree of multimerization. rvWF from all cells was also shown to bind to purified FVIII and in this case binding appeared to be independent of the degree of multimerization. We conclude that whereas vWF is naturally synthesized only by endothelial cells and megakaryocytes, it can be expressed in a biologically active form from various other cell types.


Acta Naturae ◽  
2016 ◽  
Vol 8 (2) ◽  
pp. 79-86 ◽  
Author(s):  
P. V. Elizar’ev ◽  
D. V. Lomaev ◽  
D. A. Chetverina ◽  
P. G. Georgiev ◽  
M. M. Erokhin

Maintenance of the individual patterns of gene expression in different cell types is required for the differentiation and development of multicellular organisms. Expression of many genes is controlled by Polycomb (PcG) and Trithorax (TrxG) group proteins that act through association with chromatin. PcG/TrxG are assembled on the DNA sequences termed PREs (Polycomb Response Elements), the activity of which can be modulated and switched from repression to activation. In this study, we analyzed the influence of transcriptional read-through on PRE activity switch mediated by the yeast activator GAL4. We show that a transcription terminator inserted between the promoter and PRE doesnt prevent switching of PRE activity from repression to activation. We demonstrate that, independently of PRE orientation, high levels of transcription fail to dislodge PcG/TrxG proteins from PRE in the absence of a terminator. Thus, transcription is not the main factor required for PRE activity switch.


2018 ◽  
Vol 23 (46) ◽  
pp. 7109-7120
Author(s):  
Vasiliki Tsigkou ◽  
Gerasimos Siasos ◽  
Evanthia Bletsa ◽  
Maria-Paraskevi Panoilia ◽  
Angeliki Papastavrou ◽  
...  

Background: Numerous studies indicate that statins have multiple beneficial actions (known as ‘pleiotropic actions&#39;) on cardiovascular system through the improvement of endothelial dysfunction, inflammation, oxidative stress, excessive arterial thrombosis, and stabilization of the atherosclerotic plaque. Aortic disease primarily consists of aortic valve stenosis, aortic valve regurgitation, aneurysm disease, and genetic disorders such as Marfan syndrome, bicuspid aortic valve and aortic coarctation. Many studies have revealed the cardioprotective actions of statins in aortic disease. </P><P> Objective: Our aim was to present current data concerning the value of treatment with statins in aortic diseases. </P><P> Methods: A thorough search of PubMed and the Cochrane Database was conducted to identify the studies and novel articles related to the use of statins in aortic disease. </P><P> Results: Numerous studies in animals and humans indicate a beneficial effect of treatment with statins in the previous conditions apart from a few conflicting data. </P><P> Conclusion: There is a need of further investigation in this field, especially for the estimation of the optimal type and dose of statins required in each clinical condition of aortic disease.


2020 ◽  
Vol 19 (4) ◽  
pp. 248-256
Author(s):  
Yangmin Zheng ◽  
Ziping Han ◽  
Haiping Zhao ◽  
Yumin Luo

Conclusion: Stroke is a complex disease caused by genetic and environmental factors, and its etiological mechanism has not been fully clarified yet, which brings great challenges to its effective prevention and treatment. MAPK signaling pathway regulates gene expression of eukaryotic cells and basic cellular processes such as cell proliferation, differentiation, migration, metabolism and apoptosis, which are considered as therapeutic targets for many diseases. Up to now, mounting evidence has shown that MAPK signaling pathway is involved in the pathogenesis and development of ischemic stroke. However, the upstream kinase and downstream kinase of MAPK signaling pathway are complex and the influencing factors are numerous, the exact role of MAPK signaling pathway in the pathogenesis of ischemic stroke has not been fully elucidated. MAPK signaling molecules in different cell types in the brain respond variously after stroke injury, therefore, the present review article is committed to summarizing the pathological process of different cell types participating in stroke, discussed the mechanism of MAPK participating in stroke. We further elucidated that MAPK signaling pathway molecules can be used as therapeutic targets for stroke, thus promoting the prevention and treatment of stroke.


Viruses ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 257
Author(s):  
Zuzanna Drulis-Kawa ◽  
Barbara Maciejewska

Biofilms are a community of surface-associated microorganisms characterized by the presence of different cell types in terms of physiology and phenotype [...]


2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Dvir Gur ◽  
Emily J. Bain ◽  
Kory R. Johnson ◽  
Andy J. Aman ◽  
H. Amalia Pasoili ◽  
...  

AbstractSkin color patterns are ubiquitous in nature, impact social behavior, predator avoidance, and protection from ultraviolet irradiation. A leading model system for vertebrate skin patterning is the zebrafish; its alternating blue stripes and yellow interstripes depend on light-reflecting cells called iridophores. It was suggested that the zebrafish’s color pattern arises from a single type of iridophore migrating differentially to stripes and interstripes. However, here we find that iridophores do not migrate between stripes and interstripes but instead differentiate and proliferate in-place, based on their micro-environment. RNA-sequencing analysis further reveals that stripe and interstripe iridophores have different transcriptomic states, while cryogenic-scanning-electron-microscopy and micro-X-ray diffraction identify different crystal-arrays architectures, indicating that stripe and interstripe iridophores are different cell types. Based on these results, we present an alternative model of skin patterning in zebrafish in which distinct iridophore crystallotypes containing specialized, physiologically responsive, organelles arise in stripe and interstripe by in-situ differentiation.


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