scholarly journals Human Vascular Pericytes and Cytomegalovirus Pathobiology

2019 ◽  
Vol 20 (6) ◽  
pp. 1456 ◽  
Author(s):  
Donald Alcendor
Keyword(s):  
Endothelial Cells ◽  
Fluid Transport ◽  
Hcmv Infection ◽  
Vascular System ◽  
Vascular Inflammation ◽  
Lytic Replication ◽  
Blood Retinal Barrier ◽  
Potential Harm ◽  
Multipotent Cells ◽  
Subclinical Vascular Disease

Pericytes are multipotent cells of the vascular system with cytoplasmic extensions proximal to endothelial cells that occur along the abluminal surface of the endothelium. The interactions between endothelial cells and pericytes are essential for proper microvascular formation, development, stabilization, and maintenance. Pericytes are essential for the regulation of paracellular flow between cells, transendothelial fluid transport, angiogenesis, and vascular immunosurveillance. They also influence the chemical composition of the surrounding microenvironment to protect endothelial cells from potential harm. Dysregulation or loss of pericyte function can result in microvascular instability and pathological consequences. Human pericytes have been shown to be targets for human cytomegalovirus (HCMV) infection and lytic replication that likely contribute to vascular inflammation. This review focuses on human vascular pericytes and their permissiveness for HCMV infection. It also discusses their implication in pathogenesis in the blood–brain barrier (BBB), the inner blood–retinal barrier (IBRB), the placenta–blood barrier, and the renal glomerulus as well as their potential role in subclinical vascular disease.

Increased mitochondrial H2O2 production promotes endothelial NF-κB activation in aged rat arteries

2007 ◽  
Vol 293 (1) ◽  
pp. H37-H47 ◽  
Author(s):  
Zoltan Ungvari ◽  
Zsuzsanna Orosz ◽  
Nazar Labinskyy ◽  
Aracelie Rivera ◽  
Zhao Xiangmin ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Endothelial Cells ◽  
Vascular System ◽  
Vascular Inflammation ◽  
Luciferase Reporter ◽  
H2o2 Production ◽  
Luciferase Reporter Gene ◽  
Mitochondrial Oxidative Stress ◽  
Gene Assay

Previous studies have shown that the aging vascular system undergoes pro-atherogenic phenotypic changes, including increased oxidative stress and a pro-inflammatory shift in endothelial gene expression profile. To elucidate the link between increased oxidative stress and vascular inflammation in aging, we compared the carotid arteries and aortas of young and aged (24 mo old) Fisher 344 rats. In aged vessels there was an increased NF-κB activity (assessed by luciferase reporter gene assay and NF-κB binding assay), which was attenuated by scavenging H2O2. Aging did not alter the vascular mRNA and protein expression of p65 and p50 subunits of NF-κB. In endothelial cells of aged vessels there was an increased production of H2O2 (assessed by 5,6-chloromethyl-2′,7′-dichlorodihydrofluorescein diacetate-acetyl ester fluorescence), which was attenuated by the mitochondrial uncoupler FCCP. In young arteries and cultured endothelial cells, antimycin A plus succinate significantly increased FCCP-sensitive mitochondrial H2O2 generation, which was associated with activation of NF-κB. In aged vessels inhibition of NF-κB (by pyrrolidenedithiocarbamate, resveratrol) significantly attenuated inflammatory gene expression and inhibited monocyte adhesiveness. Thus increased mitochondrial oxidative stress contributes to endothelial NF-κB activation, which contributes to the pro-inflammatory phenotypic alterations in the aged vaculature. Our model predicts that by reducing mitochondrial H2O2 production and/or directly inhibiting NF-κB novel anti-aging pharmacological treatments (e.g., calorie restriction mimetics) will exert significant anti-inflammatory and vasoprotective effects.

scholarly journals Interleukin-6 Trans-Signaling Mediated Regulation of Paracellular Permeability in Human Retinal Endothelial Cells

2021 ◽  
Vol 1 (2) ◽  
pp. 137-153
Author(s):  
Joshua Glass ◽  
Rebekah Robinson ◽  
Tae-Jin Lee ◽  
Ashok Sharma ◽  
Shruti Sharma
Keyword(s):  
Gene Expression ◽  
Endothelial Cells ◽  
Diabetic Retinopathy ◽  
Interleukin 6 ◽  
Vascular Inflammation ◽  
Paracellular Permeability ◽  
Blood Retinal Barrier ◽  
Retinal Endothelial Cells ◽  
Expression Of Genes ◽  
Signaling Activation

Long-term hyperglycemia-mediated oxidative stress and inflammation lead to the blood-retinal barrier (BRB) dysfunction and increased vascular permeability associated with diabetic retinopathy (DR). Interleukin-6 (IL-6) is one of the primary mediators of retinal vascular inflammation. IL-6 signaling through its membrane-bound IL-6 receptor is known as classical signaling, and through a soluble IL-6 receptor (sIL-6R) is known as trans-signaling. Increasing evidence suggests that classical signaling is primarily anti-inflammatory, whereas trans-signaling induces the pro-inflammatory effects of IL-6. The purpose of this study was to compare the effects of these two pathways on paracellular permeability and expression of genes involved in inter-endothelial junctions in human retinal endothelial cells (HRECs). IL-6 trans-signaling activation caused significant disruption to paracellular integrity, with increased paracellular permeability, and was associated with significant changes in gene expression related to adherens, tight, and gap junctions. IL-6 classical signaling did not alter paracellular resistance in HRECs and had no distinct effects on gene expression. In conclusion, IL-6 trans-signaling, but not classical signaling, is a major mediator of the increased paracellular permeability characteristic of inner BRB breakdown in diabetic retinopathy. This study also identified potential inter-endothelial junction genes involved in the IL-6 trans-signaling mediated regulation of paracellular permeability in HRECs.

Abstract 482: IDH2 Deficiency Induces Oxidative Stress and Vascular Inflammation

2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Seonhee Kim ◽  
Su-jeong Choi ◽  
Harsha Nagar ◽  
Shuyu Piao ◽  
Ikjun Lee ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endothelial Cells ◽  
Mitochondrial Dysfunction ◽  
Vascular Function ◽  
Vascular System ◽  
Vascular Inflammation ◽  
No Production ◽  
Mitochondrial Superoxide ◽  
Isocitrate Dehydrogenase 2 ◽  
Enos Phosphorylation

Isocitrate dehydrogenase 2 (IDH2) plays an essential role protecting cells against oxidative stress-induced damage. A deficiency in IDH2 leads to mitochondrial dysfunction and the production of reactive oxygen species (ROS) in cardiomyocytes and endothelial cells. However, the physiological function of IDH2 in vascular system is mostly unknown In this study, we investigated whether IDH2 knockdown causes mitochondrial dysfunction and vascular inflammation in vitro and in vivo . IDH2 knockdown decreased the expression of mitochondrial oxidative phosphorylation (OXPHOS) complexes I, II and III, which lead to increased mitochondrial superoxide. In addition, the levels of fission and fusion proteins (Mfn-1, OPA-1, and Drp-1) were significantly altered and MnSOD expression also was decreased by IDH2 knockdown. Furthermore, knockdown of IDH2 decreased eNOS phosphorylation and nitric oxide (NO) concentration in endothelial cells. Interestingly, treatment with Mito-TEMPO, a mitochondrial-specific superoxide scavenger, recovered mitochondrial fission-fusion imbalance and blunted mitochondrial superoxide production, and reduced the IDH2 knockdown-induced decrease in MnSOD expression, eNOS phosphorylation and NO production in endothelial cells. Endothelium-dependent vasorelaxation was impaired, and the concentration of bioavailable NO decreased in the aortic ring in IDH2 knockout mice. These findings suggest that IDH2 deficiency induces endothelial dysfunction through the induction of dynamic mitochondrial changes and impairment in vascular function. Key words: IDH2, mitochondria, endothelial cells, ROS

Lasertechniques treatment of vascular malformations

Phlebologie ◽  
2010 ◽  
Vol 39 (03) ◽  
pp. 167-175
Author(s):  
M. Poetke ◽  
P. Urban ◽  
H.-P. Berlien
Keyword(s):  
Endothelial Cells ◽  
Spontaneous Regression ◽  
Vascular System ◽  
Vascular Malformations ◽  
Clinical Importance ◽  
Vascular Structure ◽  
Laser Application ◽  
Vascular Morphogenesis ◽  
Structural Abnormalities

SummaryVascular malformations are structural abnormalities, errors of vascular morphogenesis, which can be localized in all parts of the vascular system. All vascular malformations by definition, are present at birth and grow proportionately with the child; their volume can change. In contrast to the haemangiomas, which only proliferate from the endothelial cells the division in stages is of clinical importance. Vascular malformations are divided from the part of vascular system, which is affected.In principle the techniques of laser application in congenital vascular tumours like haemangiomas and in vascular malformations are similar, but the aim is different. In tumours the aim is to induce regression, in vascular malformations the aim is to destroy the pathologic vascular structure because there is no spontaneous regression. This means that the parameters for treatment of vascular malformations must be more aggressive than for vascular tumours.

scholarly journals Studying dynamic stress effects on the behaviour of THP-1 cells by microfluidic channels

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Semra Zuhal Birol ◽  
Rana Fucucuoglu ◽  
Sertac Cadirci ◽  
Ayca Sayi-Yazgan ◽  
Levent Trabzon
Keyword(s):  
Endothelial Cells ◽  
Shear Stress ◽  
Vascular System ◽  
Circulatory System ◽  
Disease Process ◽  
Microfluidic Channels ◽  
Shear Stresses ◽  
Stress Effects ◽  
Adhesion Behavior ◽  
Cycling System

AbstractAtherosclerosis is a long-term disease process of the vascular system that is characterized by the formation of atherosclerotic plaques, which are inflammatory regions on medium and large-sized arteries. There are many factors contributing to plaque formation, such as changes in shear stress levels, rupture of endothelial cells, accumulation of lipids, and recruitment of leukocytes. Shear stress is one of the main factors that regulates the homeostasis of the circulatory system; therefore, sudden and chronic changes in shear stress may cause severe pathological conditions. In this study, microfluidic channels with cavitations were designed to mimic the shape of the atherosclerotic blood vessel, where the shear stress and pressure difference depend on design of the microchannels. Changes in the inflammatory-related molecules ICAM-1 and IL-8 were investigated in THP-1 cells in response to applied shear stresses in an continuous cycling system through microfluidic channels with periodic cavitations. ICAM-1 mRNA expression and IL-8 release were analyzed by qRT-PCR and ELISA, respectively. Additionally, the adhesion behavior of sheared THP-1 cells to endothelial cells was examined by fluorescence microscopy. The results showed that 15 Pa shear stress significantly increases expression of ICAM-1 gene and IL-8 release in THP-1 cells, whereas it decreases the adhesion between THP-1 cells and endothelial cells.

scholarly journals Vascular Inflammation Is Associated with Loss of Aquaporin 1 Expression on Endothelial Cells and Increased Fluid Leakage in SARS-CoV-2 Infected Golden Syrian Hamsters

Viruses ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 639
Author(s):  
Lisa Allnoch ◽  
Georg Beythien ◽  
Eva Leitzen ◽  
Kathrin Becker ◽  
Franz-Josef Kaup ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Vascular Inflammation ◽  
Intercellular Junctions ◽  
Edema Formation ◽  
Vascular Integrity ◽  
Syrian Hamsters ◽  
Aquaporin 1 ◽  
Vascular Walls ◽  
Transmission Electron ◽  
Mock Infection

Vascular changes represent a characteristic feature of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection leading to a breakdown of the vascular barrier and subsequent edema formation. The aim of this study was to provide a detailed characterization of the vascular alterations during SARS-CoV-2 infection and to evaluate the impaired vascular integrity. Groups of ten golden Syrian hamsters were infected intranasally with SARS-CoV-2 or phosphate-buffered saline (mock infection). Necropsies were performed at 1, 3, 6, and 14 days post-infection (dpi). Lung samples were investigated using hematoxylin and eosin, alcian blue, immunohistochemistry targeting aquaporin 1, CD3, CD204, CD31, laminin, myeloperoxidase, SARS-CoV-2 nucleoprotein, and transmission electron microscopy. SARS-CoV-2 infected animals showed endothelial hypertrophy, endothelialitis, and vasculitis. Inflammation mainly consisted of macrophages and lower numbers of T-lymphocytes and neutrophils/heterophils infiltrating the vascular walls as well as the perivascular region at 3 and 6 dpi. Affected vessels showed edema formation in association with loss of aquaporin 1 on endothelial cells. In addition, an ultrastructural investigation revealed disruption of the endothelium. Summarized, the presented findings indicate that loss of aquaporin 1 entails the loss of intercellular junctions resulting in paracellular leakage of edema as a key pathogenic mechanism in SARS-CoV-2 triggered pulmonary lesions.

scholarly journals Poldip2 controls leukocyte infiltration into the ischemic brain by regulating focal adhesion kinase-mediated VCAM-1 induction

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Lori N. Eidson ◽  
Qingzeng Gao ◽  
Hongyan Qu ◽  
Daniel S. Kikuchi ◽  
Ana Carolina P. Campos ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cerebral Ischemia ◽  
Focal Adhesion Kinase ◽  
Adhesion Molecules ◽  
Focal Adhesion ◽  
Vascular Inflammation ◽  
Leukocyte Recruitment ◽  
Ischemic Brain ◽  
Inflammatory Monocytes

AbstractStroke is a multiphasic process involving a direct ischemic brain injury which is then exacerbated by the influx of immune cells into the brain tissue. Activation of brain endothelial cells leads to the expression of adhesion molecules such vascular cell adhesion molecule 1 (VCAM-1) on endothelial cells, further increasing leukocyte recruitment. Polymerase δ-interacting protein 2 (Poldip2) promotes brain vascular inflammation and leukocyte recruitment via unknown mechanisms. This study aimed to define the role of Poldip2 in mediating vascular inflammation and leukocyte recruitment following cerebral ischemia. Cerebral ischemia was induced in Poldip2+/+ and Poldip2+/− mice and brains were isolated and processed for flow cytometry or RT-PCR. Cultured rat brain microvascular endothelial cells were used to investigate the effect of Poldip2 depletion on focal adhesion kinase (FAK)-mediated VCAM-1 induction. Poldip2 depletion in vivo attenuated the infiltration of myeloid cells, inflammatory monocytes/macrophages and decreased the induction of adhesion molecules. Focusing on VCAM-1, we demonstrated mechanistically that FAK activation was a critical intermediary in Poldip2-mediated VCAM-1 induction. In conclusion, Poldip2 is an important mediator of endothelial dysfunction and leukocyte recruitment. Thus, Poldip2 could be a therapeutic target to improve morbidity following ischemic stroke.

Increased hemangioblast commitment, not vascular disorganization, is the primary defect in flt-1 knock-out mice

Development ◽  
1999 ◽  
Vol 126 (13) ◽  
pp. 3015-3025 ◽  
Author(s):  
G.H. Fong ◽  
L. Zhang ◽  
D.M. Bryce ◽  
J. Peng
Keyword(s):  
Endothelial Cells ◽  
Population Density ◽  
Cell Fate ◽  
Vascular System ◽  
Primitive Streak ◽  
Cellular Level ◽  
Wild Type ◽  
Primary Defect ◽  
Knock Out ◽  
Vascular Channels

We previously demonstrated the essential role of the flt-1 gene in regulating the development of the cardiovascular system. While the inactivation of the flt-1 gene leads to a very severe disorganization of the vascular system, the primary defect at the cellular level was unknown. Here we report a surprising finding that it is an increase in the number of endothelial progenitors that leads to the vascular disorganization in flt-1(−/−) mice. At the early primitive streak stage (prior to the formation of blood islands), hemangioblasts are formed much more abundantly in flt-1(−/−) embryos. This increase is primarily due to an alteration in cell fate determination among mesenchymal cells, rather than to increased proliferation, migration or reduced apoptosis of flt-1(−/−) hemangioblasts. We further show that the increased population density of hemangioblasts is responsible for the observed vascular disorganization, based on the following observations: (1) both flt-1(−/−) and flt-1(+/+) endothelial cells formed normal vascular channels in chimaeric embryos; (2) wild-type endothelial cells formed abnormal vascular channels when their population density was significantly increased; and (3) in the absence of wild-type endothelial cells, flt-1(−/−) endothelial cells alone could form normal vascular channels when sufficiently diluted in a developing embryo. These results define the primary defect in flt-1(−/−) embryos at the cellular level and demonstrate the importance of population density of progenitor cells in pattern formation.

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