Injury of the renal microvascular endothelium alters barrier function after ischemia

2003 ◽  
Vol 285 (2) ◽  
pp. F191-F198 ◽  
Author(s):  
Timothy A. Sutton ◽  
Henry E. Mang ◽  
Silvia B. Campos ◽  
Ruben M. Sandoval ◽  
Mervin C. Yoder ◽  
...  
Keyword(s):  
Cell Injury ◽  
Ischemia Reperfusion Injury ◽  
Morphological Changes ◽  
Ischemia Reperfusion ◽  
Endothelial Injury ◽  
Microvascular Endothelial Cell ◽  
Vascular Endothelial ◽  
Microvascular Endothelium ◽  
Renal Microvasculature ◽  
Microvascular Endothelial

The role of renal microvascular endothelial cell injury in the pathophysiology of ischemic acute renal failure (ARF) remains largely unknown. No consistent morphological alterations have been ascribed to the endothelium of the renal microvasculature as a result of ischemia-reperfusion injury. Therefore, the purpose of this study was to examine biochemical markers of endothelial injury and morphological changes in the renal microvascular endothelium in a rodent model of ischemic ARF. Circulating von Willebrand factor (vWF) was measured as a marker of endothelial injury. Twenty-four hours after ischemia, circulating vWF peaked at 124% over baseline values ( P = 0.001). The FVB-TIE2/GFP mouse was utilized to localize morphological changes in the renal microvascular endothelium. Immediately after ischemia, there was a marked increase in F-actin aggregates in the basal and basolateral aspect of renal microvascular endothelial cells in the corticomedullary junction. After 24 h of reperfusion, the pattern of F-actin staining was more similar to that observed under physiological conditions. In addition, alterations in the integrity of the adherens junctions of the renal microvasculature, as demonstrated by loss of localization in vascular endothelial cadherin immunostaining, were observed after 24 h of reperfusion. This observation temporally correlated with the greatest extent of permeability defect in the renal microvasculature as identified using fluorescent dextrans and two-photon intravital imaging. Taken together, these findings indicate that renal vascular endothelial injury occurs in ischemic ARF and may play an important role in the pathophysiology of ischemic ARF.

scholarly journals Small Interfering RNA Efficiently Suppresses Adhesion Molecule Expression on Pulmonary Microvascular Endothelium

2011 ◽  
Vol 2011 ◽  
pp. 1-10 ◽  
Author(s):  
Tobias Walker ◽  
Julian Siegel ◽  
Andrea Nolte ◽  
Silke Hartmann ◽  
Angela Kornberger ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Adhesion Molecule ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Microvascular Endothelial Cells ◽  
Adhesion Molecule Expression ◽  
Small Interfering Rnas ◽  
Sirna Transfection ◽  
Microvascular Endothelium ◽  
Microvascular Endothelial

Background. Adhesion molecules are known to influence postoperative organ function, they are hardly involved in the inflammatory response following the ischemia-reperfusion injury. We sought to investigate the potency of small interfering RNAs to suppress adhesion molecule expression in human pulmonary microvascular endothelial cells.Methods. Human lung microvascular endothelial cells were transfected with specific siRNA followed by a stimulation of the cells with an inflammatory cytokine. Adhesion molecule expression was determined by FACS-analysis, and reduction of intracellular mRNA was determined by qRT-PCR. Furthermore, the attachment of isolated neutrophils on the endothelial layer was determined after siRNA transfection.Results. In summary, siRNA transfection significantly decreased the percentage positive cells in a single cocktail transfection of each adhesion molecule investigated. Adhering neutrophils were diminished as well.Conclusion. siRNA might be a promising tool for the effective suppression of adhesion molecule expression on pulmonary microvascular cells, potentially minimizing leukocyte-endothelial depending interactions of a pulmonary allograft.

scholarly journals Resveratrol regulates cytokine secretion by cardiac microvascular endothelium under hypoxia/reoxygenation condition

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
H Cui ◽  
Y J Yang ◽  
W J Zong
Keyword(s):  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Peak Effect ◽  
Cellular Growth ◽  
Dependent Manner ◽  
Microvascular Endothelium ◽  
National Budget ◽  
Cytokine Profiles ◽  
Microvascular Endothelial ◽  
Hypoxia Reoxygenation

Abstract Background Microvascular endothelial injury is recently considered playing an initial role in myocardial ischemia/reperfusion injury (MIRI). Cardiac microvascular endothelial cells (CMECs) regulate cardiomyocytes and haematocytes via secreting cytokine. MIRI jeopardize not only the barrier function but also the paracrine function of microvasculature. Resveratrol, a natural polyphenolic compound, was demonstrated to protect myocardium against MIRI and to preserve the function of endothelium. However, how the paracrine function of CMECs is regulated by MIRI and resveratrol remains to be elucidated. Purpose The study was to illuminate the alteration of cytokine profiles secreted by CMECs under hypoxia/reoxygenation (H/R) condition and its modulation by resveratrol. Methods CMECs were exposed to different concentrations of resveratrol for 30 minutes and then were subjected to H/R for 12 h/2 h. Apoptotic rates were measured to determine the optimal concentration. Protein antibody arrays were performed to find the alteration of cytokine secreted into conditioned medium by CMECs. A Gene Ontology (GO) analysis was applied to interpret the functional implication of changes in cytokine profiles. Results Resveratrol inhibited apoptosis of CMECs in a dose-dependent manner after H/R and reached its peak effect at the concentration of 100μM, which reduced apoptosis from 27.27±2.95% to 15.01±1.36% (Figure 1A and B). The results of a cluster analysis and all significantly altered factors are shown in figure 1C (fold-change >1.5; p<0.05). Twenty-nine types of cytokine were significantly changed by H/R (15 factors decreased and 14 increased, Figure 2A), and resveratrol at 100μM changed 98 types of cytokine compared with the H/R group (93 factors decreased and 5 increased, Figure 2B). Among these cytokine, eight factors were increased by H/R and they were decreased by resveratrol. Eleven were attenuated by H/R and further decreased by resveratrol. Insulin-like growth factor binding protein-1 was up-regulated by H/R and it was further increased by resveratrol (Figure 2C). The factors with significant alteration were involved in cellular growth, proliferation and differentiation, as well as chemotaxis and transport. Conclusions Resveratrol inhibited the apoptosis of CMECs and modulated the paracrine function of cardiac microvascular endothelium under ischemia/reperfusion condition. FUNDunding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Natural Science Foundation Figure 1 Figure 2

scholarly journals Role of xanthine oxidase and granulocytes in ischemia-reperfusion injury

1988 ◽  
Vol 255 (6) ◽  
pp. H1269-H1275 ◽  
Author(s):  
D. N. Granger
Keyword(s):  
Hydrogen Peroxide ◽  
Xanthine Oxidase ◽  
Superoxide Anion ◽  
Cell Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Microvascular Endothelium ◽  
Ischemic Period ◽  
Membrane Components

In this lecture, evidence is presented to support the following hypothesis regarding the roles of xanthine oxidase-derived oxidants and granulocytes in ischemia-reperfusion-induced microvascular injury. During the ischemic period, ATP is catabolized to yield hypoxanthine. The hypoxic stress also triggers the conversion of NAD-reducing xanthine dehydrogenase to the oxygen radical-producing xanthine oxidase. During reperfusion, molecular oxygen is reintroduced into the tissue where it reacts with hypoxanthine and xanthine oxidase to produce a burst of superoxide anion and hydrogen peroxide. In the presence of iron, superoxide anion and hydrogen peroxide react via the Haber-Weiss reaction to form hydroxyl radicals. This highly reactive and cytotoxic radical then initiates lipid peroxidation of cell membrane components and the subsequent release of substances that attract, activate, and promote the adherence of granulocytes to microvascular endothelium. The adherent granulocytes then cause further endothelial cell injury via the release of superoxide and various proteases.

scholarly journals H2S Pretreatment Is Promigratory and Decreases Ischemia/Reperfusion Injury in Human Microvascular Endothelial Cells

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Elisa Zicola ◽  
Elisa Arrigo ◽  
Daniele Mancardi
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Reperfusion Injury ◽  
Vascular Function ◽  
Cell Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Endothelial Cell Migration ◽  
Microvascular Endothelial Cells ◽  
Microvascular Endothelial

Endothelial cell injury and vascular function strongly correlate with cardiac function following ischemia/reperfusion injury. Several studies indicate that endothelial cells are more sensitive to ischemia/reperfusion compared to cardiomyocytes and are critical mediators of cardiac ischemia/reperfusion injury. H2S is involved in the regulation of cardiovascular system homeostasis and can act as a cytoprotectant during ischemia/reperfusion. Activation of ERK1/2 in endothelial cells after H2S stimulation exerts an enhancement of angiogenesis while its inhibition significantly decreases H2S cardioprotective effects. In this work, we investigated how H2S pretreatment for 24 hours prevents the ischemia/reperfusion injury and promotes angiogenesis on microvascular endothelial cells following an ischemia/reperfusion protocol in vitro, using a hypoxic chamber and ischemic buffer to simulate the ischemic event. H2S preconditioning positively affected cell viability and significantly increased endothelial cell migration when treated with 1 μM H2S. Furthermore, mitochondrial function was preserved when cells were preconditioned. Since ERK1/2 phosphorylation was extremely enhanced in ischemia/reperfusion condition, we inhibited ERK both directly and indirectly to verify how H2S triggers this pathway in endothelial cells. Taken together, our data suggest that H2S treatment 24 hours before the ischemic insult protects endothelial cells from ischemia/reperfusion injury and eventually decreases myocardial injury.

Role of calcium-independent phospholipase A2 in complement-mediated glomerular epithelial cell injury

2008 ◽  
Vol 294 (3) ◽  
pp. F469-F479 ◽  
Author(s):  
Daniel Cohen ◽  
Joan Papillon ◽  
Lamine Aoudjit ◽  
Hongping Li ◽  
Andrey V. Cybulsky ◽  
...  
Keyword(s):  
Epithelial Cell ◽  
Cell Injury ◽  
Ischemia Reperfusion Injury ◽  
Morphological Changes ◽  
Ischemia Reperfusion ◽  
Prostaglandin E ◽  
Glomerular Epithelial Cell ◽  
Novel Approach

In experimental membranous nephropathy, complement C5b-9-induced glomerular epithelial cell (GEC) injury leads to morphological changes in GEC and proteinuria, in association with phospholipase A2 (PLA2) activation. The present study addresses the role of calcium-independent PLA2 (iPLA2) in GEC injury. iPLA2β short and iPLA2γ were expressed in cultured rat GEC and normal rat glomeruli. To determine whether iPLA2 is involved in complement-mediated arachidonic acid (AA) release, GEC were stably transfected with iPLA2γ or iPLA2β cDNAs (GEC-iPLA2γ; GEC-iPLA2β). Compared with control cells (GEC-Neo), GEC-iPLA2γ and GEC-iPLA2β demonstrated greater expression of iPLA2 proteins and activities. Complement-mediated release of [3H]AA was augmented significantly in GEC-iPLA2γ compared with GEC-Neo, and the augmented [3H]AA release was inhibited by the iPLA2-directed inhibitor bromoenol lactone (BEL). For comparison, overexpression of iPLA2γ also amplified [3H]AA release after incubation of GEC with H2O2, or chemical anoxia followed by reexposure to glucose (in vitro ischemia-reperfusion injury). In parallel with release of [3H]AA, complement-mediated production of prostaglandin E2 was amplified in GEC-iPLA2γ. Complement-mediated cytotoxicity was attenuated significantly in GEC-iPLA2γ compared with GEC-Neo, and the cytoprotective effect of iPLA2γ was reversed by BEL, and in part by indomethacin. Overexpression of iPLA2β did not amplify complement-dependent [3H]AA release, but nonetheless attenuated complement-mediated cytotoxicity. Thus iPLA2γ may be involved in complement-mediated release of AA. Expression of iPLA2γ or iPLA2β induces cytoprotection against complement-dependent GEC injury. Modulation of iPLA2 activity may prove to be a novel approach to reducing GEC injury.

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