Abstract 27: ApoA-I Improves Lymphatic Function Through a Platelet-Dependent Mechanism in Atherosclerotic Mice

2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Andreea Milasan ◽  
François Dallaire ◽  
Gabriel Jean ◽  
Jean-Claude Tardif ◽  
Yahye Merhi ◽  
...  
Keyword(s):  
Lymphatic Vessel ◽  
Ex Vivo ◽  
Lymphatic Vessels ◽  
Lymphatic Transport ◽  
Lv Function ◽  
Experimental Conditions ◽  
Lymphatic Function ◽  
Beneficial Effects ◽  
Dependent Mechanism

Rationale: Lymphatic vessels (LVs) are now recognized as prerequisite players in the modulation of cholesterol removal from the artery wall in experimental conditions of plaque regression, and a particular attention has been brought on the role of the collecting LVs in early atherosclerosis-related lymphatic dysfunction. Whereas recent findings revealed that apoA-I restores the neovascularization capacity of the lymphatic system during tumor necrosis factor-induced inflammation, the effect of apoA-I on collecting LV function during atherosclerosis has not been tested. Objective: In the present study, we address whether and how apoA-I can enhance collecting LV function in atherosclerosis-associated lymphatic dysfunction. Methods and Results: A 6-week systemic treatment with lipid-free apoA-I enhanced lymphatic transport and abrogated collecting lymphatic vessel permeability in atherosclerotic Ldlr –/– mice when compared to control. As injection of apoA-I has been shown to protect wild-type mice against flow restriction-induced thrombosis, and that platelets are identified as key elements in the maintenance of lymphatic vessel integrity via their interaction with lymphatic endothelial cells (LECs), we have tested whether the effects of apoA-I could be mediated through a platelet-dependent mechanism. Our in vivo results show that apoA-I kinetics in lymph reflected that of blood. Ex vivo experiments performed with washed platelets isolated from mouse blood reveal that apoA-I decreased thrombin-induced but not podoplanin-induced platelet aggregation. Whereas this result suggests that apoA-I limits platelet thrombotic potential in blood but not in lymph, we demonstrate that treatment of human LECs with apoA-I increases the adhesion of bridge-like platelets on human LECs. Conclusions: Our results suggest that apoA-I can mediate beneficial effects on lymphatic function by promoting platelet adhesion to the lymphatic endothelium and consequently restore collecting LV integrity. Altogether, we bring forward a new pleiotropic role for apoA-I in lymphatic function and unveil new potential therapeutic targets for the prevention and treatment of atherosclerosis.

Abstract 569: Lymphatic Function Is Impaired Before Atherosclerosis Onset in a Model of Atherosclerosis-prone Mice

2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Andreea Milasan ◽  
Marie-Elaine Clavet-Lanthier ◽  
Gaetan Mayer ◽  
Catherine Martel
Keyword(s):  
Lymphatic Vessel ◽  
Lymphatic Vessels ◽  
Ldl Receptor ◽  
Atherosclerotic Lesion ◽  
Lymphatic Transport ◽  
Cellular Transport ◽  
Aortic Sinus ◽  
Lymphatic Function ◽  
Preliminary Results ◽  
Atherosclerosis Progression

Introduction: Macrophages and cholesterol are the two main constituents driving the inflammatory response that characterizes atherosclerosis. In a recent study, the lymphatic system has been identified as a novel prerequisite player in the removal of cholesterol out of the atherosclerotic lesion. It has been shown that without a functional lymphatic network, cholesterol gets trapped in the artery wall. The lymphatic vessels are composed of two main components, namely the absorptive capillaries, responsible for the uptake of the cells, molecules and fluid, and the collecting vessels, characterized by pumping units (lymphangions) that are propelling the lymphatic content toward the blood circulation in a unidirectional manner. The relative roles of the lymphatic capillaries and collectors in the context of atherosclerotic disease are still unclear. Methods and results: Lymphatic function has been evaluated in 3-month old atherosclerosis-prone (LDLR-/-; hApoB100+/+, also called ATX mice), LDLR-/-, atherosclerosis-protected (PCSK9-/- mice, deficient in a convertase that induces the degradation of the LDL receptor) and wild-type (WT) mice. Our preliminary data show that, like LDLR-/- mice, pre-atherosclerotic ATX mice exhibit impaired lymphatic cellular transport. Immunohistochemistry and immunofluorescence imaging portrays a relatively normal number of sprouting and diameter of lymphatic vessel capillaries in the adventitial layer of the aortic sinus and in the skin dermis of ATX mice compared to WT or PCSK9-/- animals. Conclusions: Our preliminary results suggest that lymphatic transport is impaired even before the onset of atherosclerosis, and that i) the LDLR is associated with lymphatic vessel function, and that ii) the collecting lymphatic vessels are most likely responsible for the impairment in lymphatic dysfunction in LDLR-/- and ATX mice. These preliminary results suggest that characterizing the functional pumping capacity of the collecting vessels would be a prerequisite in understanding the interplay between atherosclerosis progression and lymphatic transport. We hope that in the long run we will be able to identify new therapeutic targets to enhance lymphatic transport and ultimately limit atherosclerosis progression.

Phenolic Acids Exert Anticholinesterase and Cognition-Improving Effects

2018 ◽  
Vol 15 (6) ◽  
pp. 531-543 ◽  
Author(s):  
Dominik Szwajgier ◽  
Ewa Baranowska-Wojcik ◽  
Kamila Borowiec
Keyword(s):  
Phenolic Acids ◽  
Ex Vivo ◽  
Amyloid Β ◽  
Inhibitory Effect ◽  
In Vivo Studies ◽  
Amyloid Β Peptide ◽  
Beneficial Effects ◽  
Aβ Fibrils

Numerous authors have provided evidence regarding the beneficial effects of phenolic acids and their derivatives against Alzheimer's disease (AD). In this review, the role of phenolic acids as inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) is discussed, including the structure-activity relationship. In addition, the inhibitory effect of phenolic acids on the formation of amyloid β-peptide (Aβ) fibrils is presented. We also cover the in vitro, ex vivo, and in vivo studies concerning the prevention and treatment of the cognitive enhancement.

Factors affecting in vitro and in vivo antioxidant effects. Experimental conditions and nature of oxidants determine antioxidant efficacy

2021 ◽  
pp. 1-9
Author(s):  
Etsuo Niki
Keyword(s):  
Biological Molecules ◽  
Experimental Conditions ◽  
Factors Affecting ◽  
Beneficial Effects ◽  
Multiple Oxidants ◽  
Antioxidant Effects

Reactive oxygen and nitrogen species have been implicated in the onset and progression of various diseases and the role of antioxidants in the maintenance of health and prevention of diseases has received much attention. The action and effect of antioxidants have been studied extensively under different reaction conditions in multiple media. The antioxidant effects are determined by many factors. This review aims to discuss several important issues that should be considered for determination of experimental conditions and interpretation of experimental results in order to understand the beneficial effects and limit of antioxidants against detrimental oxidation of biological molecules. Emphasis was laid on cell culture experiments and effects of diversity of multiple oxidants on antioxidant efficacy.

scholarly journals Computational Investigation of Transmural Differences in Left Ventricular Contractility

2016 ◽  
Vol 138 (11) ◽  
Author(s):  
Hua Wang ◽  
Xiaoyan Zhang ◽  
Shauna M. Dorsey ◽  
Jeremy R. McGarvey ◽  
Kenneth S. Campbell ◽  
...  
Keyword(s):  
Myocardial Contractility ◽  
Ex Vivo ◽  
Experimental Studies ◽  
Contractile Force ◽  
Left Ventricular ◽  
Lv Function ◽  
Fe Model ◽  
Myocardial Layers ◽  
Best Fit

Myocardial contractility of the left ventricle (LV) plays an essential role in maintaining normal pump function. A recent ex vivo experimental study showed that cardiomyocyte force generation varies across the three myocardial layers of the LV wall. However, the in vivo distribution of myocardial contractile force is still unclear. The current study was designed to investigate the in vivo transmural distribution of myocardial contractility using a noninvasive computational approach. For this purpose, four cases with different transmural distributions of maximum isometric tension (Tmax) and/or reference sarcomere length (lR) were tested with animal-specific finite element (FE) models, in combination with magnetic resonance imaging (MRI), pressure catheterization, and numerical optimization. Results of the current study showed that the best fit with in vivo MRI-derived deformation was obtained when Tmax assumed different values in the subendocardium, midmyocardium, and subepicardium with transmurally varying lR. These results are consistent with recent ex vivo experimental studies, which showed that the midmyocardium produces more contractile force than the other transmural layers. The systolic strain calculated from the best-fit FE model was in good agreement with MRI data. Therefore, the proposed noninvasive approach has the capability to predict the transmural distribution of myocardial contractility. Moreover, FE models with a nonuniform distribution of myocardial contractility could provide a better representation of LV function and be used to investigate the effects of transmural changes due to heart disease.

Abstract 5368: Igf +hgf Enhance Sca-1 + /cd31 − Cell Therapy in Hearts with Postinfarction Lv Remodeling

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Xiaohong Wang ◽  
Elizabeth Braunlin ◽  
Qingsong Hu ◽  
Joseph Lee ◽  
Qinglu Li ◽  
...  
Keyword(s):  
Growth Factor ◽  
Cell Survival ◽  
Cell Transplantation ◽  
Cellular Therapy ◽  
Contractile Function ◽  
Lv Function ◽  
Beneficial Effects ◽  
Myocardial Bioenergetics

Insulin-like growth factor 1 (IGF-1) and hepatocyte growth factor (HGF) are two potent cell survival factors in response to hypoxia and oxidative stress. We have previously shown that transplantation of Sca-1 + /CD31 − cells can improve LV function in hearts with acute myocardial infarction (AMI) although the engraftment rate was low. We hypothesized that supplementation of IGF-1 and HGF at delivery of cellular therapy can enhance the beneficial effects of Sca-1 + /CD31 − cells in the injured heart by increasing engraftment rate and endogenous cardiac cell survival. Adenovirus nuclear LacZ-labeled Sca-1 + /CD31 − cells (1x10 6 ) were injected into the ischemic area after LAD ligation in BalbC mice. Recombinant mouse IGF-1+HGF (100ng) was added to the cell suspension prior to the injection. The LV function (ECHO) and in vivo myocardial bioenergetics ( 31 P-NMR spectroscopy) were assessed 4 weeks after AMI and cell transplantation. Normal mice (Normal, n=6), and 2 control groups of LAD ligation (MI, n=6), and MI plus Sca-1 + /CD31 − cell transplantation (Cell, n=6), were compared to AMI mice with Sca-1 + /CD31 − cells transplantation plus IGF-1+HGF (Cell+IGF-1+HGF, n=6). Sca-1 + /CD31 − cells formed viable grafts and improved LV contractile function (EF: Control, 53.3+/−3.2; MI, 18.9+/−3.9; Cell, 29.1+/−5.1, p<0.05) and myocardial bioenergetics (PCr/ATP: Control, 2.13+/−0.09; MI, 1.21+/−0.09; Cell, 1.72+/−0.12; p<0.01). IGF+HGF significantly further enhanced the benefits of the cell transplantation as evidenced by significantly increased EF to 38.3+/−3.1% (p<0.05), which was accompanied by a higher cell engraftment rate (p<0.05). Using the in vitro co culture of Sca-1 + /CD31 − cells with HL-1 cells labeled by Vybrant CFDA SE cell tracer kit, we observed both IGF+HGF and Sca-1 + /CD31 − cells can inhibit TNFα and hypoxia induced HL-1 cell apoptosis (Control, 7+/−1%; TNFα, 24+/−1%; IGF+HGF+TNFα, 10+/−1%; n=6, P<0.001) and caspase 3 expression. These data demonstrate that IGF-1+HGF could serve as an adjuvant to cell transplantation for myocardial restoration.

scholarly journals Metformin-stimulated AMPK-α1 promotes microvascular repair in acute lung injury

2013 ◽  
Vol 305 (11) ◽  
pp. L844-L855 ◽  
Author(s):  
Ming-Yuan Jian ◽  
Mikhail F. Alexeyev ◽  
Paul E. Wolkowicz ◽  
Jaroslaw W. Zmijewski ◽  
Judy R. Creighton
Keyword(s):  
Endothelial Cells ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Ex Vivo ◽  
Endothelial Permeability ◽  
Beneficial Effects ◽  
Isolated Lung

Acute lung injury secondary to sepsis is a leading cause of mortality in sepsis-related death. Present therapies are not effective in reversing endothelial cell dysfunction, which plays a key role in increased vascular permeability and compromised lung function. AMP-activated protein kinase (AMPK) is a molecular sensor important for detection and mediation of cellular adaptations to vascular disruptive stimuli. In this study, we sought to determine the role of AMPK in resolving increased endothelial permeability in the sepsis-injured lung. AMPK function was determined in vivo using a rat model of endotoxin-induced lung injury, ex vivo using the isolated lung, and in vitro using cultured rat pulmonary microvascular endothelial cells (PMVECs). AMPK stimulation using N1-(α-d-ribofuranosyl)-5-aminoimidizole-4-carboxamide or metformin decreased the LPS-induced increase in permeability, as determined by filtration coefficient ( Kf) measurements, and resolved edema as indicated by decreased wet-to-dry ratios. The role of AMPK in the endothelial response to LPS was determined by shRNA designed to decrease expression of the AMPK-α1 isoform in capillary endothelial cells. Permeability, wounding, and barrier resistance assays using PMVECs identified AMPK-α1 as the molecule responsible for the beneficial effects of AMPK in the lung. Our findings provide novel evidence for AMPK-α1 as a vascular repair mechanism important in the pulmonary response to sepsis and identify a role for metformin treatment in the management of capillary injury.

Different mechanisms in the attachment of cells to native and denatured collagen

1979 ◽  
Vol 38 (1) ◽  
pp. 267-281
Author(s):  
S.L. Schor ◽  
J. Court
Keyword(s):  
Cell Attachment ◽  
Experimental Conditions ◽  
Cell Matrix ◽  
Matrix Interactions ◽  
Independent Mechanism ◽  
Cell Matrix Interactions ◽  
Serum Dependent ◽  
Kinetics Of ◽  
Dependent Mechanism

The attachment of cells to collagen has been reported previously to require the presence of serum and the particular serum protein involved in this process, variously known as CIG, CAP or fibronectin, has been isolated. This conclusion that cell attachment to collagen requires serum (or more precisely, fibronectin) is based on experiments measuring the kinetics of cell attachment to films of collagen. We have measured the kinetics of attachment of HeLa and attachment to films of collagen-containing substrata under a variety of experimental conditions and present evidence that the serum-dependent mechanism of cell attachment described by others is actually only the case for films of denatured collagen, while cell attachment to native collagen fibres occurs by a different, serum-independent, mechanism. The possible relevance of these findings to cell-matrix interactions in vivo is discussed.

scholarly journals Regulation of cilia abundance in multiciliated cells

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Rashmi Nanjundappa ◽  
Dong Kong ◽  
Kyuhwan Shim ◽  
Tim Stearns ◽  
Steven L Brody ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Surface Area ◽  
Ex Vivo ◽  
Compensatory Mechanism ◽  
Multiciliated Cells ◽  
Culture Model ◽  
A Cell ◽  
Dependent Mechanism

Multiciliated cells (MCC) contain hundreds of motile cilia used to propel fluid over their surface. To template these cilia, each MCC produces between 100-600 centrioles by a process termed centriole amplification. Yet, how MCC regulate the precise number of centrioles and cilia remains unknown. Airway progenitor cells contain two parental centrioles (PC) and form structures called deuterosomes that nucleate centrioles during amplification. Using an ex vivo airway culture model, we show that ablation of PC does not perturb deuterosome formation and centriole amplification. In contrast, loss of PC caused an increase in deuterosome and centriole abundance, highlighting the presence of a compensatory mechanism. Quantification of centriole abundance in vitro and in vivo identified a linear relationship between surface area and centriole number. By manipulating cell size, we discovered that centriole number scales with surface area. Our results demonstrate that a cell-intrinsic surface area-dependent mechanism controls centriole and cilia abundance in multiciliated cells.

scholarly journals Detection of the Strains Induced in Murine Tibias by Ex Vivo Uniaxial Loading with Different Sensors

Sensors ◽  
2019 ◽  
Vol 19 (23) ◽  
pp. 5109
Author(s):  
Emanuele Rizzuto ◽  
Barbara Peruzzi ◽  
Mariagrazia Giudice ◽  
Enrica Urciuoli ◽  
Erika Pittella ◽  
...  
Keyword(s):  
Standard Deviation ◽  
Ex Vivo ◽  
Mean Value ◽  
Uniaxial Loading ◽  
Image Correlation ◽  
Strain Gauges ◽  
Experimental Conditions ◽  
The Mean

In this paper, the characterization of the main techniques and transducers employed to measure local and global strains induced by uniaxial loading of murine tibiae is presented. Micro strain gauges and digital image correlation (DIC) were tested to measure local strains, while a moving coil motor-based length transducer was employed to measure relative global shortening. Local strain is the crucial parameter to be measured when dealing with bone cell mechanotransduction, so we characterized these techniques in the experimental conditions known to activate cell mechanosensing in vivo. The experimental tests were performed using tibia samples excised from twenty-two C57BL/6 mice. To evaluate measurement repeatability we computed the standard deviation of ten repetitive compressions to the mean value. This value was lower than 3% for micro strain gauges, and in the range of 7%–10% for DIC and the length transducer. The coefficient of variation, i.e., the standard deviation to the mean value, was about 35% for strain gauges and the length transducer, and about 40% for DIC. These results provided a comprehensive characterization of three methodologies for local and global bone strain measurement, suggesting a possible field of application on the basis of their advantages and limitations.

scholarly journals Dietary compounds as potential modulators of microRNA expression in psoriasis

2019 ◽  
Vol 10 ◽  
pp. 204062231986480 ◽  
Author(s):  
Hristina Kocic ◽  
Giovanni Damiani ◽  
Bojana Stamenkovic ◽  
Michael Tirant ◽  
Andrija Jovic ◽  
...  
Keyword(s):  
Vitamin D ◽  
Omega 3 ◽  
Experimental Conditions ◽  
Keratinocyte Proliferation ◽  
Methyl Donors ◽  
Beneficial Effects ◽  
Small Noncoding Rnas ◽  
The Impact

Nutrigenomic DNA reprogramming in different chronic diseases and cancer has been assessed through the stimulation of gene expression and mRNA synthesis versus DNA silencing by CpG DNA modification (methylation); histone modification (acetylation, methylation) and expression of small noncoding RNAs, known as microRNAs (miRNAs). With regard to the specific nutrigenomic effects in psoriasis, the influence of specific diets on inflammatory cell signaling transcriptional factors such as nuclear factor (NF)-κB and Wnt signaling pathways, on disease-related specific cytokine expression, pro/antioxidant balance, keratinocyte proliferation/apoptosis and on proliferation/differentiation ratio have been documented; however, the influence of dietary compounds on the balance between ‘good and bad’ miRNA expression has not been considered. This review aims to summarize knowledge about aberrant microRNAs expression in psoriasis and to emphasize the potential impact of some dietary compounds on endogenous miRNA synthesis in experimental conditions in vivo and in vitro. Among the aberrantly expressed miRNAs in psoriasis, one of the most prominently upregulated seems to be miR-21. The beneficial effects of phenolic compounds (curcumin and resveratrol), vitamin D, methyl donors, and omega-3 fatty acids (eicosapentaenoic acid and docosahexaenoic acid) are discussed. Highly expressed miR-155 has been downregulated by flavonoids (through a quercetin-rich diet) and by vitamin D. Quercetin has been effective in modulating miR-146a. On the other hand, downregulated miR-125b expression was restored by vitamin D, Coenzyme Q10 and by microelement selenium. In conclusion, the miRNA profile, together with other ‘omics’, may constitute a multifaceted approach to explore the impact of diet on psoriasis prevention and treatment.

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