scholarly journals Vascular underpinning of COVID-19

Open Biology ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. 200208 ◽  
Author(s):  
Vanessa Wazny ◽  
Anthony Siau ◽  
Kan Xing Wu ◽  
Christine Cheung
Keyword(s):  
Vascular Dysfunction ◽  
Cellular Heterogeneity ◽  
Management Guidelines ◽  
Alternative Pathways ◽  
Cellular Models ◽  
Host Cell Surface ◽  
Vascular Beds ◽  
Microvascular Inflammation ◽  
Endothelial Dysfunctions ◽  
Primary Phenomenon

COVID-19 management guidelines have largely attributed critically ill patients who develop acute respiratory distress syndrome, to a systemic overproduction of pro-inflammatory cytokines. Cardiovascular dysfunction may also represent a primary phenomenon, with increasing data suggesting that severe COVID-19 reflects a confluence of vascular dysfunction, thrombosis and dysregulated inflammation. Here, we first consolidate the information on localized microvascular inflammation and disordered cytokine release, triggering vessel permeability and prothrombotic conditions that play a central role in perpetuating the pathogenic COVID-19 cascade. Secondly, we seek to clarify the gateways which SARS-CoV-2, the causative COVID-19 virus, uses to enter host vascular cells. Post-mortem examinations of patients' tissues have confirmed direct viral endothelial infection within several organs. While there have been advances in single-cell RNA sequencing, endothelial cells across various vascular beds express low or undetectable levels of those touted SARS-CoV-2 entry factors. Emerging studies postulate alternative pathways and the apicobasal distribution of host cell surface factors could influence endothelial SARS-CoV-2 entry and replication. Finally, we provide experimental considerations such as endothelial polarity, cellular heterogeneity in organoids and shear stress dynamics in designing cellular models to facilitate research on viral-induced endothelial dysfunctions. Understanding the vascular underpinning of COVID-19 pathogenesis is crucial to managing outcomes and mortality.

scholarly journals High-cholesterol diet during pregnancy induces maternal vascular dysfunction in mice: potential role for oxidized LDL-induced LOX-1 and AT1 receptor activation

2020 ◽  
Vol 134 (17) ◽  
pp. 2295-2313
Author(s):  
Tamara Sáez ◽  
Floor Spaans ◽  
Raven Kirschenman ◽  
Tatsuya Sawamura ◽  
Sandra T. Davidge
Keyword(s):  
Vascular Function ◽  
Vascular Dysfunction ◽  
Oxidized Ldl ◽  
Receptor Activation ◽  
Adverse Outcomes ◽  
High Cholesterol Diet ◽  
Cholesterol Diet ◽  
High Cholesterol ◽  
Uterine Arteries ◽  
Vascular Beds

Abstract The lectin-like oxidized low-density-lipoprotein (oxLDL) receptor-1 (LOX-1) has been shown to induce angiotensin II (AngII) type 1 receptor (AT1) activation, contributing to vascular dysfunction. Preeclampsia is a pregnancy complication characterized by vascular dysfunction and increased LOX-1 and AT1 activation; however, whether LOX-1 and AT1 activity contributes to vascular dysfunction in preeclampsia is unknown. We hypothesized that increased oxLDL levels during pregnancy lead to LOX-1 activation and subsequent AT1 activation, resulting in vascular dysfunction. Pregnant wild-type (WT) and transgenic LOX-1 overexpressing (LOX-1tg) mice were fed a control diet (CD) or high-cholesterol diet (HCD, to impair vascular function) between gestational day (GD) 13.5-GD18.5. On GD18.5, AngII-induced vasoconstriction and methylcholine (MCh)-induced endothelium-dependent vasodilation responses were assessed in aortas and uterine arteries. HCD decreased fetal weight and increased circulating oxLDL/cholesterol levels in WT, but not in LOX-1tg mice. HCD did not alter AngII responsiveness or AT1 expression in both vascular beds; however, AngII responsiveness and AT1 expression were lower in aortas from LOX-1tg compared with WT mice. In aortas from WT-CD mice, acute oxLDL exposure induced AT1-mediated vasoconstriction via LOX-1. HCD impaired endothelium-dependent vasodilation and increased superoxide levels in WT aortas, but not uterine arteries. Moreover, in WT-CD mice oxLDL decreased MCh sensitivity in both vascular beds, partially via LOX-1. In summary, HCD impaired pregnancy outcomes and vascular function, and oxLDL-induced LOX-1 activation may contribute to vascular dysfunction via AT1. Our study suggests that LOX-1 could be a potential target to prevent adverse outcomes associated with vascular dysfunction in preeclampsia.

scholarly journals Spatial single-cell profiling of intracellular metabolomes in situ

2019 ◽  
Author(s):  
Luca Rappez ◽  
Mira Stadler ◽  
Sergio Triana ◽  
Prasad Phapale ◽  
Mathias Heikenwalder ◽  
...  
Keyword(s):  
Single Cell ◽  
Lipid Droplets ◽  
Spatial Information ◽  
Cellular Heterogeneity ◽  
Cell Contact ◽  
Cell Monolayers ◽  
Cellular Models ◽  
Single Cell Profiling ◽  
Cell Cell

SummaryThe recently unveiled extent of cellular heterogeneity demands for single-cell investigations of intracellular metabolomes to reveal their roles in intracellular processes, molecular microenvironment and cell-cell interactions. To address this, we developed SpaceM, a method for in situ spatial single-cell metabolomics of cell monolayers which detects >100 metabolites in >10000 individual cells together with fluorescence and morpho-spatial cellular features. We discovered that the intracellular metabolomes of co-cultured human HeLa cells and mouse NIH3T3 fibroblasts predict the cell type with 90.4% accuracy and revealed a short-distance metabolic intermixing between HeLa and NIH3T3. We characterized lipid classes composing lipid droplets in steatotic differentiated human hepatocytes, and discovered a preferential accumulation of long-chain phospholipids, a co-regulation of oleic and linoleic acids, and an association of phosphatidylinositol monophosphate with high cell-cell contact. SpaceM provides single-cell metabolic, phenotypic, and spatial information and enables spatio-molecular investigations of intracellular metabolomes in a variety of cellular models.

scholarly journals Effective reconstruction of functional organotypic kidney spheroid for in vitro nephrotoxicity studies

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Hyun Mi Kang ◽  
Jung Hwa Lim ◽  
Kyung Hee Noh ◽  
Dongmin Park ◽  
Hyun-Soo Cho ◽  
...  
Keyword(s):  
Proximal Tubule ◽  
Renal Toxicity ◽  
Structural Complexity ◽  
Cellular Heterogeneity ◽  
Cellular Models ◽  
Functional Aspects ◽  
Distal Tubules ◽  
Immortalized Cell ◽  
Cellular Compartments

AbstractStable and reproducible kidney cellular models could accelerate our understanding of diseases, help therapeutics development, and improve nephrotoxicity screenings. Generation of a reproducible in vitro kidney models has been challenging owing to the cellular heterogeneity and structural complexity of the kidney. We generated mixed immortalized cell lines that stably maintained their characteristic expression of renal epithelial progenitor markers for the different lineages of kidney cellular compartments via the BMP7 signaling pathway from a mouse and a human whole kidney. These cells were used to generate functional and matured kidney spheroids containing multiple renal lineages, such as the proximal tubule, loop of Henle, distal tubules, and podocytes, using extracellular matrix and physiological force, named spheroid-forming unit (SFU). They expressed all apical and basolateral transporters that are important for drug metabolism and displayed key functional aspects of the proximal tubule, including protein endocytosis and increased gamma-glutamyltransferase activity, and cyclic AMP responded to external cues, such as parathyroid hormone. Following exposure, cells fluxed and took up drugs via proximal tubule-specific apical or basolateral transporters, and displayed increased cell death and expression of renal injury marker. Here, we developed a new differentiation method to generate kidney spheroids that structurally recapitulate important features of the kidney effectively and reproducibly using mixed immortalized renal cells, and showed their application for renal toxicity studies.

Sites of Adsorption of the Bacteriophages T3 and T5 on the Wall of Escherichia Coli B.

1967 ◽  
Vol 25 ◽  
pp. 96-97
Author(s):  
Manfred E. Bayer
Keyword(s):  
Escherichia Coli ◽  
Cell Wall ◽  
Electron Microscope ◽  
Uranyl Acetate ◽  
E Coli ◽  
Receptor Sites ◽  
Rigid Cell Wall ◽  
Host Cell Surface ◽  
Bacterial Viruses ◽  
Escherichia Coli B

Bacterial viruses adsorb specifically to receptors on the host cell surface. Although the chemical composition of some of the cell wall receptors for bacteriophages of the T-series has been described and the number of receptor sites has been estimated to be 150 to 300 per E. coli cell, the localization of the sites on the bacterial wall has been unknown.When logarithmically growing cells of E. coli are transferred into a medium containing 20% sucrose, the cells plasmolize: the protoplast shrinks and becomes separated from the somewhat rigid cell wall. When these cells are fixed in 8% Formaldehyde, post-fixed in OsO4/uranyl acetate, embedded in Vestopal W, then cut in an ultramicrotome and observed with the electron microscope, the separation of protoplast and wall becomes clearly visible, (Fig. 1, 2). At a number of locations however, the protoplasmic membrane adheres to the wall even under the considerable pull of the shrinking protoplast. Thus numerous connecting bridges are maintained between protoplast and cell wall. Estimations of the total number of such wall/membrane associations yield a number of about 300 per cell.

An ultrastructural analysis of the sympathetic innervation of the rabbit ear artery and middle cerebral artery and their branches

1992 ◽  
Vol 50 (1) ◽  
pp. 934-935
Author(s):  
John T. Dodge ◽  
John A. Bevan
Keyword(s):  
Middle Cerebral Artery ◽  
Cerebral Artery ◽  
Sympathetic Innervation ◽  
Electrical Field Stimulation ◽  
Rabbit Ear Artery ◽  
Electrical Field ◽  
Functional Differences ◽  
Ear Artery ◽  
Rabbit Ear ◽  
Vascular Beds

Unlike many peripheral vascular beds, the sympathetic nervous system exerts little control on cerebral blood flow. The contractile response of isolated rabbit middle cerebral artery (MCA) segments to electrical field stimulation of its intramural nerves is less than in a similar-sized artery from the ear. This study was undertaken to characterize and compare the perivascular neuromuscular relationships and innervation density of similar-sized arteries varying in diameter from these two different regional arterial beds to see if there were structural correlates for these functional differences.

Gene expression during two alternative pathways of ovary development in Pisum sativum: fruit development and ovary senescence

1992 ◽  
Vol 85 (1) ◽  
pp. 69-76 ◽  
Author(s):  
Maria-Jose Sanchez-Beltran ◽  
Juan Carbonell ◽  
Jose L. Garcia-Martinez ◽  
Isabel Lopez-Diaz
Keyword(s):  
Gene Expression ◽  
Pisum Sativum ◽  
Fruit Development ◽  
Ovary Development ◽  
Alternative Pathways ◽  
Ovary Senescence

Adrenergic Stimulation of Regional Plasminogen Activator Release in Rabbits

1992 ◽  
Vol 68 (05) ◽  
pp. 545-549 ◽  
Author(s):  
W L Chandler ◽  
S C Loo ◽  
D Mornin
Keyword(s):  
Lower Extremity ◽  
Plasminogen Activator ◽  
Beta Blocker ◽  
Time Course ◽  
Vascular System ◽  
Adrenergic Stimulation ◽  
Epinephrine Administration ◽  
Adrenergic Antagonist ◽  
Vascular Beds ◽  
Stimulation Of

SummaryThe purpose of this study was to determine whether different regions of the rabbit vascular system show variations in the rate of plasminogen activator (PA) secretion. To start, we evaluated the time course, dose response and adrenergic specificity of PA release. Infusion of 1 µg/kg of epinephrine stimulated a 116 ± 60% (SD) increase in PA activity that peaked 30 to 60 s after epinephrine administration. Infusion of 1 µg/kg of norepinephrine, isoproterenol and phenylephrine had no effect on PA activity. Pretreatment with phentolamine, an alpha adrenergic antagonist, blocked the release of PA by epinephrine while pretreatment with the beta blocker propranolol had no effect. This suggests that PA release in the rabbit was mediated by some form of alpha receptor.Significant arterio-venous differences in basal PA activity were found across the pulmonary and splanchnic vascular beds but not the lower extremity/pelvic bed. After stimulation with epinephrine, PA activity increased 46% across the splanchnic bed while no change was seen across the lower extremity/pelvic bed. We conclude that several vascular beds contribute to circulating PA activity in the rabbit, and that these beds secrete PA at different rates under both basal and stimulated conditions.

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