scholarly journals Macrophages in Atherosclerosis, First or Second Row Players?

Biomedicines ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 1214
Author(s):  
Eloïse Checkouri ◽  
Valentin Blanchard ◽  
Olivier Meilhac

Macrophages represent a cell type that has been widely described in the context of atherosclerosis since the earliest studies in the 17th century. Their role has long been considered to be preponderant in the onset and aggravation of atherosclerosis, in particular by participating in the establishment of a chronic inflammatory state by the release of pro-inflammatory cytokines and by uncontrolled engorgement of lipids resulting in the formation of foam cells and later of the necrotic core. However, recent evidence from mouse models using an elegant technique of tracing vascular smooth muscle cells (VSMCs) during plaque development revealed that resident VSMCs display impressive plastic properties in response to an arterial injury, allowing them to switch into different cell types within the plaque, including mesenchymal-like cells, macrophage-like cells and osteochondrogenic-like cells. In this review, we oppose the arguments in favor or against the influence of macrophages versus VSMCs in all stages of atherosclerosis including pre-atherosclerosis, formation of lipid-rich foam cells, development of the necrotic core and the fibrous cap as well as calcification and rupture of the plaque. We also analyze the relevance of animal models for the investigation of the pathophysiological mechanisms of atherosclerosis in humans, and discuss potential therapeutic strategies targeting either VSMCs or macrophage to prevent the development of cardiovascular events. Overall, although major findings have been made from animal models, efforts are still needed to better understand and therefore prevent the development of atherosclerotic plaques in humans.

RMD Open ◽  
2018 ◽  
Vol 4 (2) ◽  
pp. e000744 ◽  
Author(s):  
Kerstin Klein

The reading of acetylation marks on histones by bromodomain (BRD) proteins is a key event in transcriptional activation. Small molecule inhibitors targeting bromodomain and extra-terminal (BET) proteins compete for binding to acetylated histones. They have strong anti-inflammatory properties and exhibit encouraging effects in different cell types in vitro and in animal models resembling rheumatic diseases in vivo. Furthermore, recent studies that focus on BRD proteins beyond BET family members are discussed.


1985 ◽  
Vol 101 (4) ◽  
pp. 1442-1454 ◽  
Author(s):  
P Cowin ◽  
H P Kapprell ◽  
W W Franke

Desmosomal plaque proteins have been identified in immunoblotting and immunolocalization experiments on a wide range of cell types from several species, using a panel of monoclonal murine antibodies to desmoplakins I and II and a guinea pig antiserum to desmosomal band 5 protein. Specifically, we have taken advantage of the fact that certain antibodies react with both desmoplakins I and II, whereas others react only with desmoplakin I, indicating that desmoplakin I contains unique regions not present on the closely related desmoplakin II. While some of these antibodies recognize epitopes conserved between chick and man, others display a narrow species specificity. The results show that proteins whose size, charge, and biochemical behavior are very similar to those of desmoplakin I and band 5 protein of cow snout epidermis are present in all desmosomes examined. These include examples of simple and pseudostratified epithelia and myocardial tissue, in addition to those of stratified epithelia. In contrast, in immunoblotting experiments, we have detected desmoplakin II only among cells of stratified and pseudostratified epithelial tissues. This suggests that the desmosomal plaque structure varies in its complement of polypeptides in a cell-type specific manner. We conclude that the obligatory desmosomal plaque proteins, desmoplakin I and band 5 protein, are expressed in a coordinate fashion but independently from other differentiation programs of expression such as those specific for either epithelial or cardiac cells.


2006 ◽  
Vol 06 (02) ◽  
pp. 187-204 ◽  
Author(s):  
JAGANNATHAN LAKSHMIPATHY ◽  
WIESLAW L. NOWINSKI ◽  
ERIC A. WERNERT

Different isocontour extraction methods use different cell types (tetrahedral, hexahedral, etc.) depending on the nature of the acquisition grids (structured, unstructured, etc.). The existing isocontouring methods have the following pre-steps for the actual extraction process: (a) identification of cell types, (b) identification of topologically independent instances for each cell type, (c) determination of surface primitives contained in the topologically independent instances and (d) generation of a lookup table such that the name of the entry is an instance of a cell and the entry is the triangle set for that instance. The extraction process outputs the triangles from the lookup table. In this paper we present a novel generic method that enables us to list topologically independent surface primitives called "templates" within any n-polytope cell namely tetrahedra, hexahedra etc. We have also modified the traditional lookup table such that name is the cell instance and the entry is face index representations of all template instances contained in that cell. To show an example, we have applied this approach on a hexahedron and listed the templates and subsequently we have showed how to construct a lookup table. Most modern graphics hardware render triangles faster if they are rendered collectively as triangle strips as opposed to individual triangles. With our modified lookup table approach we can identify triangles in the neighboring cell in a linear time and hence we are able to connect two triangle strips into a longer triangle strip on the fly during the extraction process. We have compared our approach with some existing methods. The following are some of the important features of the method: (1) Simplicity, (2) procedural triangulation and (3) face-index representation.


1988 ◽  
Vol 106 (6) ◽  
pp. 2023-2033 ◽  
Author(s):  
S A Lewis ◽  
N J Cowan

In the accompanying paper (Gu, W., S. A. Lewis, and N. J. Cowan. 1988. J. Cell Biol. 106: 2011-2022), we report the generation of three antisera, each of which uniquely recognizes a different mammalian alpha-tubulin isotype, plus a fourth antibody that distinguishes between microtubules containing the tyrosinated and nontyrosinated form of the only known mammalian alpha-tubulin gene product that lacks an encoded carboxy-terminal tyrosine residue. These sera, together with five sera we raised that distinguish among the known mammalian beta-tubulin isotypes, have been used to study patterns of tubulin isotype-specific expression in muscle and testis, two tissues in which characteristic developmental changes are accompanied by dramatic rearrangements in microtubule structures. As in the case of cells in culture, there is no evidence to suggest that there is subcellular sorting of different tubulin isotypes among different kinds of microtubule, even in a cell type (the developing spermatid) that simultaneously contains such functionally distinct structures as the manchette and the flagellum. On the other hand, the patterns of expression of the various tubulin isotypes show marked and distinctive differences in different cell types and, in at least one case, evidence is presented for regulation at the translational or posttranslational level. The significance of these observations is discussed in terms of the existence of the mammalian alpha- and beta-tubulin multigene families.


2021 ◽  
Vol 42 ◽  
pp. 196-219
Author(s):  
MF Fiordalisi ◽  
◽  
AJ Silva ◽  
M Barbosa ◽  
RM Gonçalves ◽  
...  

Intervertebral disc (IVD) degeneration and the consequent low-back pain (LBP) affect over 80 % of people in western societies, constituting a tremendous socio-economic burden worldwide and largely impairing patients’ life quality. Extracellular matrix (ECM)-based scaffolds, derived from decellularised tissues, are being increasingly explored in regenerative medicine for tissue repair. Decellularisation plays an essential role for host cells and antigen removal, while maintaining native microenvironmental signals, including ECM structure, composition and mechanical properties, which are essential for driving tissue regeneration. With the lack of clinical solutions for IVD repair/regeneration, implantation of decellularised IVD tissues has been explored to halt and/or revert the degenerative cascade and the associated LBP symptoms. Over the last few years, several researchers have focused on the optimisation of IVD decellularisation methods, combining physical, chemical and enzymatic treatments, in order to successfully develop a cell-free matrix. Recellularisation of IVD-based scaffolds with different cell types has been attempted and numerous methods have been explored to address proper IVD regeneration. Herein, the advances in IVD decellularisation methods, sterilisation procedures, repopulation and biocompatibility tests are reviewed. Additionally, the importance of the donor profile for therapeutic success is also addressed. Finally, the perspectives and major hurdles for clinical use of the decellularised ECM-based biomaterials for IVD are discussed. The studies reviewed support the notion that tissue-engineering-based strategies resorting to decellularised IVD may represent a major advancement in the treatment of disc degeneration and consequent LBP.


Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Obrad R Šćepanović ◽  
Maryann Fitzmaurice ◽  
Arnold Miller ◽  
Chae-Ryon Kong ◽  
Ramachandra R Dasari ◽  
...  

Early detection and treatment of vulnerable atherosclerotic plaques, the lesions most prone to rupture, is critical to reducing patient mortality associated with cardiovascular disease. The combination of reflectance, fluorescence, and Raman spectroscopy - termed multimodal spectroscopy (MMS) - provides complementary and depth-sensitive information about tissue composition. We assessed the hypothesis that MMS can detect morphological features of vulnerable plaque: thin fibrous cap (TFC), necrotic core (NC), superficial foam cells (SFC), intralesional hemorrhage (IH), and thrombus. Methods. In vivo and ex vivo MMS spectra were collected from 12 patients undergoing peripheral vascular surgeries. The data collection was facilitated by means of a novel MMS probe catheter and a portable clinical instrument developed in our laboratory. During carotid endarterectomies, MMS spectra were collected in vivo from the intimal surface of the plaque with the probe held normal to the artery wall. During femoral bypasses, MMS spectra were collected in vivo either through the proximal anastomosis site from the posterior artery wall or adjacent to the incision. A tissue specimen was excised for additional MMS spectral collection ex vivo. Histopathological analysis was performed by a blinded cardiovascular pathologist to assess the vulnerability of each spectrally evaluated tissue site using a quantitative index based on the dimension or severity of the following: TFC, NC, SFC, IH, and thrombus. Across the total set of 76 evaluated tissue locations, MMS is shown to have the ability to detect vulnerability features including a TFC, NC or SFCs, and thrombus. A TFC is detected by measuring the relative amount of collagen assessed by fluorescence, a large NC or SFCs are detected through the combination of beta-carotene absorption and the Raman spectral signature of lipids, and thrombus is detected through its Raman signature. The results indicate that rupture-prone vulnerable plaques could be detected with a sensitivity of 96% and specificity of 72%. In conclusion, these encouraging results will help bring MMS into the clinical arena as a powerful, catheter-based diagnostic technique for early detection of vulnerable plaques.


2011 ◽  
Vol 26 (S2) ◽  
pp. 1202-1202
Author(s):  
F. Grass

Several experiments show that there is a cell to cell communicaton by light in different cell types. The most convincing experiment shows that baby hamster kidney cells can communicate their spatial orientation through a glass film, this can only happen by photon signals. If so, it can be assumed that the cells with the highest differentiation, the neurons also use this mechanism. The nervous system would have excellent conditions for a cell to cell communication by light. Neurons are large, metabolically very active (lightproducing) cells with wide arborisation, contain little pigment and are protected from ambient light by bone and connective tissue. Signal to noise ratio should be high for photon signals. It has been shown that light can be propagated along the axis tracts. Also the hollow microtubules (neurofibrillae) could act as light guiding structures. According to Jibu et al. their inner diameter of 15 nm is ideal for light guidance free of thermal noise and loss. Other findings that may be of importance in this context, are the strong flurescence properties of the major hallucinogens: LSD, bufetonine, dimethyl-tryptamine, psilocybine, psilocin, iboguanin, harmine, cannabidinol and mescaline. Furthermore it has been shown that hallucinogenic properties of these substances have a direct correlation to their fluorescence properties and their readyness to donate electrons. As hypothesis we propose that the fluorescence interacts physically with the proposed Biophoton mediated cell to cell communication thus producing hallucinations. This would be an easy and plausible explanation for the strong hallucinogenic properties of these fluorescent substances.


2000 ◽  
Vol 68 (7) ◽  
pp. 4358-4360 ◽  
Author(s):  
Maria Filippa Addis ◽  
Paola Rappelli ◽  
Pier Luigi Fiori

ABSTRACT Adhesion of Trichomonas vaginalis is believed to be dependent on four adhesion proteins, which are thought to bind to vaginal epithelial cells in a specific manner with a ligand-receptor type of interaction. However, the specific receptors on the host cell have not yet been identified. In this work, the ability of the T. vaginalis adhesins to bind to cells of different histologic derivations and from different species has been studied. HeLa, CHO, and Vero cell lines; erythrocytes from different species; and a prokaryote without a cell wall, Mycoplasma hominis, were employed in order to investigate the cell specificity of the T. vaginalis adhesins. We observed that the T. vaginalisadhesins are able to bind to the different cell types to the same extent, suggesting that the host and tissue specificity of T. vaginalis adhesion should not be due to specificity of the parasite adhesins. Our results suggest that the data published to date on the subject are probably artifactual and that the experiments reported in the literature are not appropriate for identification of protozoan adhesins.


2014 ◽  
Vol 5 (1) ◽  
Author(s):  
Sergey Rodin ◽  
Liselotte Antonsson ◽  
Colin Niaudet ◽  
Oscar E. Simonson ◽  
Elina Salmela ◽  
...  

Abstract Lack of robust methods for establishment and expansion of pluripotent human embryonic stem (hES) cells still hampers development of cell therapy. Laminins (LN) are a family of highly cell-type specific basement membrane proteins important for cell adhesion, differentiation, migration and phenotype stability. Here we produce and isolate a human recombinant LN-521 isoform and develop a cell culture matrix containing LN-521 and E-cadherin, which both localize to stem cell niches in vivo. This matrix allows clonal derivation, clonal survival and long-term self-renewal of hES cells under completely chemically defined and xeno-free conditions without ROCK inhibitors. Neither LN-521 nor E-cadherin alone enable clonal survival of hES cells. The LN-521/E-cadherin matrix allows hES cell line derivation from blastocyst inner cell mass and single blastomere cells without a need to destroy the embryo. This method can facilitate the generation of hES cell lines for development of different cell types for regenerative medicine purposes.


eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Alex de Mendoza ◽  
Hiroshi Suga ◽  
Jon Permanyer ◽  
Manuel Irimia ◽  
Iñaki Ruiz-Trillo

Cell-type specification through differential genome regulation is a hallmark of complex multicellularity. However, it remains unclear how this process evolved during the transition from unicellular to multicellular organisms. To address this question, we investigated transcriptional dynamics in the ichthyosporean Creolimax fragrantissima, a relative of animals that undergoes coenocytic development. We find that Creolimax utilizes dynamic regulation of alternative splicing, long inter-genic non-coding RNAs and co-regulated gene modules associated with animal multicellularity in a cell-type specific manner. Moreover, our study suggests that the different cell types of the three closest animal relatives (ichthyosporeans, filastereans and choanoflagellates) are the product of lineage-specific innovations. Additionally, a proteomic survey of the secretome reveals adaptations to a fungal-like lifestyle. In summary, the diversity of cell types among protistan relatives of animals and their complex genome regulation demonstrates that the last unicellular ancestor of animals was already capable of elaborate specification of cell types.


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