Serum apolipoprotein A-I depletion is causative to silica nanoparticles–induced cardiovascular damage

2021 ◽  
Vol 118 (44) ◽  
pp. e2108131118
Author(s):  
Xuting Liu ◽  
Wei Wei ◽  
Zixuan Liu ◽  
Erqun Song ◽  
Jianlin Lou ◽  
...  
Keyword(s):  
Cardiovascular Diseases ◽  
Silica Nanoparticles ◽  
Rapid Development ◽  
Atherosclerotic Lesion ◽  
Modern Science ◽  
Protein Corona ◽  
Systemic Circulation ◽  
Cardiovascular Damage ◽  
Apolipoprotein A ◽  
Mimic Peptide

The rapid development of nanotechnology has greatly benefited modern science and engineering and also led to an increased environmental exposure to nanoparticles (NPs). While recent research has established a correlation between the exposure of NPs and cardiovascular diseases, the intrinsic mechanisms of such a connection remain unclear. Inhaled NPs can penetrate the air–blood barrier from the lung to systemic circulation, thereby intruding the cardiovascular system and generating cardiotoxic effects. In this study, on-site cardiovascular damage was observed in mice upon respiratory exposure of silica nanoparticles (SiNPs), and the corresponding mechanism was investigated by focusing on the interaction of SiNPs and their encountered biomacromolecules en route. SiNPs were found to collect a significant amount of apolipoprotein A-I (Apo A-I) from the blood, in particular when the SiNPs were preadsorbed with pulmonary surfactants. While the adsorbed Apo A-I ameliorated the cytotoxic and proinflammatory effects of SiNPs, the protein was eliminated from the blood upon clearance of the NPs. However, supplementation of Apo A-I mimic peptide mitigated the atherosclerotic lesion induced by SiNPs. In addition, we found a further declined plasma Apo A-I level in clinical silicosis patients than coronary heart disease patients, suggesting clearance of SiNPs sequestered Apo A-I to compromise the coronal protein’s regular biological functions. Together, this study has provided evidence that the protein corona of SiNPs acquired in the blood depletes Apo A-I, a biomarker for prediction of cardiovascular diseases, which gives rise to unexpected toxic effects of the nanoparticles.

Apolipoprotein(a), Fibrinopeptide A and Carotid Atherosclerosis in Middle-Aged Men

1994 ◽  
Vol 72 (04) ◽  
pp. 563-566 ◽  
Author(s):  
Tuomo Rankinen ◽  
Sari Väisänen ◽  
Michele Mercuri ◽  
Rainer Rauramaa
Keyword(s):  
Risk Factors ◽  
Cardiovascular Diseases ◽  
Carotid Atherosclerosis ◽  
Intima Media Thickness ◽  
Carotid Bifurcation ◽  
Carotid Intima Media Thickness ◽  
Fibrinopeptide A ◽  
Carotid Imt ◽  
Apolipoprotein A ◽  
The Difference

SummaryThe association between apolipoprotein(a) [apo(a)], fibrinogen, fibrinopeptide A (FPA) and carotid intima-media thickness (IMT) was analyzed in Eastern Finnish men aged 50 to 60 years. Apo(a) correlated directly with carotid bifurcation (r = 0.26, p = 0.001), but not with common carotid IMT. Men in the lowest quartile of apo(a) had thinner (p = 0.013) IMT in bifurcation [1.59 mm (95% Cl 1.49; 1.68)] compared to the men in the highest [1.91 mm (95% Cl 1.73; 2.09)] apo(a) quartile. The difference remained (p=0.038) after adjusting for confounders. Plasma fibrinogen was not related to carotid IMT, whereas FPA correlated with common carotid (r = 0.21, p = 0.016) and carotid bifurcation (r = 0.21, p = 0.018) IMT. These associations abolished after adjusting for the confounders. The data suggest that apo(a) associate with carotid atherosclerosis independent of other risk factors for ischemic cardiovascular diseases.

Comparison of publication activity level in the medical field in Ukraine and the countries of the worldActivities of higher education institutions in the technology transfer

2020 ◽  
pp. 74-83
Author(s):  
A.B. Osadcha
Keyword(s):  
Web Of Science ◽  
Rapid Development ◽  
Modern Science ◽  
Modern Society ◽  
Scientific Work ◽  
Scientific Activity ◽  
Activity Level ◽  
Publication Activity ◽  
Research Progress ◽  
Medical Field

In the context of the rapid development of scientific and technological progress in Ukraine, including the medical field, a significant contribution belongs to scientific researches based on world recognition, and publications in scientific journals indexed in international bibliometric databases, will lead to the possibility of upgrading modern science in medical higher educational institutions. The most significant in modern society is not only activity process or thought, but the result that scientific research provides. Scientific activity is difficult to evaluate with only one parameter; moreover, there is a need for evaluation using qualitative indicators. The article presents author’s research results of publication activity level in the medical field in Ukraine, taking into account world experience based on international bibliometric database Clarivate Analytics’s Web of Science. Clarivate Analytics accelerates research progress by providing researchers with reliable information sources, analytics around the world, and the ability to quickly create, defend, and commercialize new ideas. Clarivate Analytics is an independent company with more than 4000 employees working in more than 100 countries, and has a well-known brand — Web of Science. It provides access to the largest database of scientific articles from carefully selected reputable journals. Researchers can use effective search instruments that take into account metadata and bibliographic references and allow you to get the highest quality, meaningful and impartial information. Web of Science is an accurate and reliable source of information for assessing scientific work, the most comprehensive resource in which both quality and quantity are equally valued.

Dynamic development of the protein corona on silica nanoparticles: composition and role in toxicity

Nanoscale ◽  
2013 ◽  
Vol 5 (14) ◽  
pp. 6372 ◽  
Author(s):  
Ninell P. Mortensen ◽  
Gregory B. Hurst ◽  
Wei Wang ◽  
Carmen M. Foster ◽  
Prakash D. Nallathamby ◽  
...  
Keyword(s):  
Silica Nanoparticles ◽  
Protein Corona ◽  
Dynamic Development

scholarly journals Artificial Cardiac Muscle with or without the Use of Scaffolds

2017 ◽  
Vol 2017 ◽  
pp. 1-15 ◽  
Author(s):  
Yifei Li ◽  
Donghui Zhang
Keyword(s):  
Tissue Engineering ◽  
Cardiovascular Diseases ◽  
Cardiac Tissue ◽  
Contractile Function ◽  
Rapid Development ◽  
Treatment Options ◽  
Cardiac Tissue Engineering ◽  
Hydrogel Scaffold ◽  
Fibrous Matrix ◽  
Advantages And Disadvantages

During the past several decades, major advances and improvements now promote better treatment options for cardiovascular diseases. However, these diseases still remain the single leading cause of death worldwide. The rapid development of cardiac tissue engineering has provided the opportunity to potentially restore the contractile function and retain the pumping feature of injured hearts. This conception of cardiac tissue engineering can enable researchers to produce autologous and functional biomaterials which represents a promising technique to benefit patients with cardiovascular diseases. Such an approach will ultimately reshape existing heart transplantation protocols. Notable efforts are accelerating the development of cardiac tissue engineering, particularly to create larger tissue with enhanced functionality. Decellularized scaffolds, polymer synthetics fibrous matrix, and natural materials are used to build robust cardiac tissue scaffolds to imitate the morphological and physiological patterns of natural tissue. This ultimately helps cells to implant properly to obtain endogenous biological capacity. However, newer designs such as the hydrogel scaffold-free matrix can increase the applicability of artificial tissue to engineering strategies. In this review, we summarize all the methods to produce artificial cardiac tissue using scaffold and scaffold-free technology, their advantages and disadvantages, and their relevance to clinical practice.

Abstract 225: Apolipoprotein A-IV Is a ß3 Integrin Ligand and an Endogenous Inhibitor of Platelets: Novel Mechanisms of Prevention and Treatment for Atherothrombosis

2014 ◽  
Vol 34 (suppl_1) ◽  
Author(s):  
Xiaohong Xu ◽  
Lining Ju ◽  
Christopher M Spring ◽  
Hong Yang ◽  
Adili Reheman ◽  
...  
Keyword(s):  
Amino Acids ◽  
Platelet Aggregation ◽  
Cardiovascular Diseases ◽  
Ex Vivo ◽  
Lipid Absorption ◽  
Endogenous Inhibitor ◽  
Inhibitory Function ◽  
Apolipoprotein A ◽  
Αiibβ3 Integrin ◽  
Human And Mouse

Apolipoprotein A-IV (apoA-IV) is a lipid binding protein secreted by the intestine during dietary lipid absorption. Several clinical studies in different ethnic populations have demonstrated that apoA-IV levels inversely correlate with cardiovascular diseases. However, the roles of apoA-IV in platelet aggregation and atherothrombosis are completely unknown. Here we isolated apoA-IV from plasma with beads coated with human platelet β3 integrin. Using a biomembrane force probe that detects single-molecule interactions, we clearly demonstrated that apoA-IV specifically binds to purified αIIbβ3 on beads and native αIIbβ3 on platelets or Chinese hamster ovary cells. ApoA-IV and αIIbβ3 interaction could be blocked by a monoclonal antibody against β 3 integrin, M1. Importantly, recombinant apoA-IV can competitively block fibrinogen-αIIbβ3 interaction, and specifically inhibited human and mouse platelet aggregation. Consistently, platelet aggregation was enhanced in mice lacking apoA-IV following stimulation with various agonists. In ex vivo perfusion chambers, apoA-IV inhibited human and mouse thrombus growth and dissolved pre-formed thrombi, while absence of apoA-IV enhanced ex vivo thrombosis under both low and high shear stresses. Furthermore, in vivo intravital microscopy models revealed that FeCl 3 - and laser-induced thrombosis were enhanced in mice lacking apoA-IV, while transfusion of human or mouse recombinant apoA-IV significantly attenuated this process. To further identify the potential binding sites of apoA-IV for platelet αIIbβ3 integrin, we deleted apoA-IV N-terminal 38 amino acids and/or the C-terminal 41 amino acids. We observed that deletion of the N-terminus abrogated platelet-inhibitory function. Interestingly, we found that mutation of either of two highly conserved aspartic acid (D) residues at positions 5 and 13 abolished or reduced the inhibitory function of apoA-IV, suggesting that D5 and/or D13 participate in a direct protein-protein interaction between apoA-IV and αIIbβ3 integrin. Thus, apoA-IV is identified as a novel endogenous inhibitor of thrombosis and represents a novel link between lipoprotein metabolism and platelet function, both of which play critical roles in cardiovascular diseases.

Student scientific circle as a form of tutor’s support

2020 ◽  
Vol 22 (4) ◽  
pp. 220-227
Author(s):  
V. I. Odin
Keyword(s):  
Soviet Union ◽  
Human Life ◽  
Rapid Development ◽  
Research Work ◽  
Modern Science ◽  
Activity Level ◽  
Imperial Russia ◽  
Scientific Circle ◽  
The Individual ◽  
Active Implementation

The concept of a student scientific circle as a form of tutor training is presented. The history of the circle movement in Russian universities of imperial Russia is analyzed, starting with the circle organized by Professor Schwartz in 1781 and continued in the Soviet Union. The data on the state support of students research work in the post-war period, including state documents of title and measures of financial support, are presented. The traditional student scientific circle is a circle of those wishing to educate themselves in addition to the planned curriculum, by conducting their own research and publishing the results. As a result, an activity-level specialist is formed from a graduate of the circle. In contrast to the traditional one, the tutor-type training circle forms the circle member as a future specialist not only at the activity level, but also at the project and, preferably, conceptual levels. Methodologically, the task of a tutor-type training circle is not only to teach the circle members the practical skills of conducting scientific research, but, first of all, in personalized work to achieve anthropological goals, to create a reasonable, creative, effective personality who can create, plan and design. In the conditions of the rapid development of modern science, the construction of the future is proceeding at a rapid pace and is associated with the active implementation of the results of scientific experiments in all aspects of human life, which requires active suppression of everyday consciousness. At the same time, due to the risk of a landslide dehumanization, the circle member, as a scientist, needs to lay down humanitarian values that define the individual as a person who shares the ideals of goodness and justice. Thus, the student scientific circle is a system in which a new generation of honest and effective scientists and high class specialists is formed under the guidance of a tutor.

Abstract 260: Apolipoprotein A-I Binding Protein Regulates Macrophage Polarization in Atherosclerosis

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Dina A Schneider ◽  
Longhou Fang ◽  
Yury I Miller
Keyword(s):  
Lipid Rafts ◽  
Lipid Accumulation ◽  
Cholesterol Efflux ◽  
Binding Protein ◽  
Macrophage Polarization ◽  
Atherosclerotic Lesion ◽  
Negative Regulator ◽  
High Cholesterol Diet ◽  
Apolipoprotein A ◽  
M1 Macrophage

Our laboratory recently demonstrated that Apolipoprotein A-I Binding Protein (AIBP), an evolutionarily conserved intracellular and secreted protein, mediates cholesterol efflux from endothelial cells, which in turn disrupts lipid rafts and limits angiogenic signaling. Since lipid rafts are implicated in multiple cell signal cascades, to better understand the in vivo role of AIBP our laboratory has generated Apoa1bp -/- mice. The Apoa1bp -/- mice exhibit increased levels of inflammatory cytokines, and have an increased content of M1 macrophages in white adipose tissue in comparison to wild type mice when challenged with a high fat diet. Since AIBP accelerates cholesterol efflux from macrophages to HDL, and vascular lipid accumulation and inflammation are key factors in atherosclerosis, we hypothesized that AIBP is atheroprotective by suppressing macrophage lipid accumulation and inflammatory M1 macrophage polarization. Immunohistochemistry shows that AIBP is present in atherosclerotic lesion macrophages. However, elicited macrophages lacking AIBP expression do not exhibit any impairment in their ability to polarize to M1, suggesting that deficiency in secreted extracellular AIBP may be responsible for the M1 phenotype observed in Apoa1bp -/- mice. Indeed, treating macrophages with recombinant AIBP prior to polarization resulted in suppression of M1 polarization. In a high-cholesterol diet feeding experiment, Apoa1bp -/- Ldlr -/- mice had increased M1 macrophage content in their aorta and aortic root atherosclerotic lesions, as determined by FACS and immunohistochemistry, respectively. In conclusion, AIBP is an important negative regulator of macrophage polarization and lipid accumulation. A better understanding of AIBP’s regulatory functions in the context of atherosclerosis will provide new mechanistic insights and targeted therapies.

Toxicity and mechanism of mesoporous silica nanoparticles in eyes

Nanoscale ◽  
2020 ◽  
Vol 12 (25) ◽  
pp. 13637-13653 ◽  
Author(s):  
Xia Chen ◽  
Shuang Zhu ◽  
Xisu Hu ◽  
Dayu Sun ◽  
Junling Yang ◽  
...  
Keyword(s):  
Mesoporous Silica ◽  
Silica Nanoparticles ◽  
Surface Area ◽  
Dry Eye ◽  
Mesoporous Silica Nanoparticles ◽  
Protein Corona ◽  
Large Surface Area ◽  
Corneal Damage

It aims to explore the toxicity and mechanism of large-surface-area MSiNPs and MSiNPs-Ag+ exposed to hCEC cells and cornea. A protein corona-based therapy was proposed to treat MSiNPs and MSiNPs-Ag+ induced corneal damage and dry eye.

Magnetite mesoporous silica nanoparticles embedded in carboxybetaine methacrylate for application in hyperthermia and drug delivery

2020 ◽  
Vol 44 (20) ◽  
pp. 8232-8240 ◽  
Author(s):  
Hasan Keshavarz ◽  
Alireza Khavandi ◽  
Somaye Alamolhoda ◽  
M. Reza Naimi-Jamal
Keyword(s):  
Drug Delivery ◽  
Mesoporous Silica ◽  
Silica Nanoparticles ◽  
Mesoporous Silica Nanoparticles ◽  
Protein Corona ◽  
Target Tissue ◽  
Burst Effect

Magnetite mesoporous silica nanoparticles (MMSNs) are biocompatible and can easily deliver a drug to the target tissue, but there are two challenges: burst effect and protein corona.

The unique lipoprotein(a): properties and immunochemical measurement

1990 ◽  
Vol 36 (12) ◽  
pp. 2019-2026 ◽  
Author(s):  
J J Albers ◽  
S M Marcovina ◽  
M S Lodge
Keyword(s):  
Rapid Development ◽  
Structural Complexity ◽  
Structural Domains ◽  
Lipoprotein A ◽  
Apolipoprotein A ◽  
High Amino Acid ◽  
Multiple Copies ◽  
High Concentrations ◽  
Size Heterogeneity ◽  
Genetically Determined

Abstract Lipoprotein (a) [Lp(a)] represents a class of lipoprotein particles defined by the presence of apolipoprotein(a), a unique glycoprotein linked by a disulfide bond to apolipoprotein B-100 to form a single macromolecule. Apolipoprotein(a) is formed by three different structural domains having high amino acid sequence homology with plasminogen. One of the domains, called kringle 4, is present in multiple copies, the number of which varies and is genetically determined. This accounts for the size heterogeneity of apolipoprotein(a) and thus of Lp(a). Because high concentrations of Lp(a) are associated with atherosclerotic cardiovascular and cerebrovascular disease and may inhibit fibrinolysis, interest in measuring Lp(a) has increased considerably, leading to a rapid development of commercially available immunoassays for the measurement of Lp(a) in human plasma. However, the immunochemical measurement of Lp(a) has several peculiar problems in addition to those encountered by the measurements of other apolipoproteins. The major problems that need to be carefully evaluated are (a) the structural complexity and heterogeneity of Lp(a), (b) the homology of apolipoprotein(a) with plasminogen, (c) the lack of standardization of the methods, and (d) the lack of a common means of expressing the Lp(a) values.

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