Nitric oxide and p38 MAP kinase mediate shear stress-dependent inhibition of MMP-2 production in microvascular endothelial cells

2006 ◽  
Vol 208 (1) ◽  
pp. 229-237 ◽  
Author(s):  
Malgorzata Milkiewicz ◽  
Cassandra Kelland ◽  
Stephen Colgan ◽  
Tara L. Haas
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
Shear Stress ◽  
Map Kinase ◽  
P38 Map Kinase ◽  
Microvascular Endothelial Cells ◽  
Dependent Inhibition ◽  
Microvascular Endothelial ◽  
Stress Dependent

MKK3 and -6-dependent activation of p38α MAP kinase is required for cytoskeletal changes in pulmonary microvascular endothelial cells induced by ICAM-1 ligation

2005 ◽  
Vol 288 (2) ◽  
pp. L359-L369 ◽  
Author(s):  
Qin Wang ◽  
Michael Yerukhimovich ◽  
William A. Gaarde ◽  
Ian J. Popoff ◽  
Claire M. Doerschuk
Keyword(s):  
Endothelial Cells ◽  
Protein Expression ◽  
Map Kinase ◽  
Neutrophil Migration ◽  
P38 Map Kinase ◽  
Cell Junctions ◽  
Microvascular Endothelial Cells ◽  
Pulmonary Microvascular Endothelial Cells ◽  
Neutrophil Adherence ◽  
Microvascular Endothelial

Previous studies demonstrated that neutrophil adherence induces ICAM-1-dependent cytoskeletal changes in TNF-α-treated pulmonary microvascular endothelial cells that are prevented by a pharmacological inhibitor of p38 MAP kinase. This study determined whether neutrophil adherence induces activation of p38 MAP kinase in endothelial cells, the subcellular localization of phosphorylated p38, which MAP kinase kinases lead to p38 activation, which p38 isoform is activated, and what the downstream targets may be. Confocal microscopy showed that neutrophil adhesion for 2 or 6 min induced an increase in phosphorylated p38 in endothelial cells that was punctate and concentrated in the central region of the endothelial cells. Studies using small interfering RNA (siRNA) to inhibit the protein expression of MAP kinase kinase 3 and 6, either singly or in combination, showed that both MAP kinase kinases were required for p38 phosphorylation. Studies using an antisense oligonucleotide to p38α demonstrated that inhibition of the protein expression of p38α 1) inhibited activation of p38 MAP kinase without affecting the protein expression of p38β; 2) prevented phosphorylation of heat shock protein 27, an actin binding protein that may induce actin polymerization upon phosphorylation; 3) attenuated cytoskeletal changes; and 4) attenuated neutrophil migration to the EC borders. Thus MAP kinase kinase3- and 6-dependent activation of the α-isoform of p38 MAP kinase is required for the cytoskeletal changes induced by neutrophil adherence and influences subsequent neutrophil migration toward endothelial cell junctions.

Shear stress increases expression of a KATP channel in rat and bovine pulmonary vascular endothelial cells

2003 ◽  
Vol 285 (4) ◽  
pp. C959-C967 ◽  
Author(s):  
Shampa Chatterjee ◽  
Abu-Bakr Al-Mehdi ◽  
Irena Levitan ◽  
Troy Stevens ◽  
Aron B. Fisher
Keyword(s):  
Endothelial Cells ◽  
Shear Stress ◽  
Membrane Depolarization ◽  
Microvascular Endothelial Cells ◽  
Adaptation Period ◽  
Pulmonary Microvascular Endothelial Cells ◽  
Channel Expression ◽  
Microvascular Endothelial ◽  
Flow Adaptation ◽  
Expression And Activity

We have shown previously that acute ischemia leads to depolarization of pulmonary microvascular endothelial cells that is prevented with cromakalim, suggesting the presence of ATP-sensitive K+ (KATP) channels in these cells. Thus KATP channel expression and activity were evaluated in rat pulmonary microvascular endothelial cells (RPMVEC) by whole cell current measurements, dot blot (mRNA), and immunoblot (protein) for the inwardly rectifying K+ channel (KIR) 6.2 subunit and fluorescent ligand binding for the sulfonylurea receptor (SUR). Low-level expression of a KATP channel was detected in endothelial cells in routine (static) culture and led us to examine whether its expression is inducible when endothelial cells are adapted to flow. Channel expression (mRNA and both KIR6.2 and SUR proteins) and inwardly rectified membrane current by patch clamp increased significantly when RPMVEC were adapted to flow at 10 dyn/cm2 for 24 h in either a parallel plate flow chamber or an artificial capillary system. Induction of the KATP channel with flow adaptation was also observed in bovine pulmonary artery endothelial cells. Flow-adapted but not static RPMVEC showed cellular plasma membrane depolarization upon stop of flow that was inhibited by a KATP channel opener and prevented by addition of cycloheximide to the medium during the flow adaptation period. These studies indicate the induction of KATP channels by flow adaptation in pulmonary endothelium and that the expression and activity of this channel are essential for the endothelial cell membrane depolarization response with acute decrease in shear stress.

scholarly journals Human brain microvascular endothelial cells resist elongation due to shear stress

2015 ◽  
Vol 99 ◽  
pp. 8-18 ◽  
Author(s):  
Adam Reinitz ◽  
Jackson DeStefano ◽  
Mao Ye ◽  
Andrew D. Wong ◽  
Peter C. Searson
Keyword(s):  
Endothelial Cells ◽  
Shear Stress ◽  
Human Brain ◽  
Microvascular Endothelial Cells ◽  
Brain Microvascular Endothelial Cells ◽  
Microvascular Endothelial

scholarly journals Lipoic acid antagonizes paraquat-induced vascular endothelial dysfunction by suppressing mitochondrial reactive oxidative stress

2019 ◽  
Vol 8 (6) ◽  
pp. 918-927 ◽  
Author(s):  
Li Pang ◽  
Ping Deng ◽  
Yi-dan Liang ◽  
Jing-yu Qian ◽  
Li-Chuan Wu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Endothelial Cells ◽  
Endothelial Dysfunction ◽  
Lipoic Acid ◽  
Microvascular Endothelial Cells ◽  
Ros Generation ◽  
Protective Effects ◽  
Migration Ability ◽  
Microvascular Endothelial

Abstract Paraquat (PQ) is a widely used herbicide in the agricultural field. The lack of an effective antidote is the significant cause of high mortality in PQ poisoning. Here, we investigate the antagonistic effects of alpha lipoic acid (α-LA), a naturally existing antioxidant, on PQ toxicity in human microvascular endothelial cells (HMEC-1). All the doses of 250, 500 and 1000 μM α-LA significantly inhibited 1000 μM PQ-induced cytotoxicity in HMEC-1 cells. α-LA pretreatment remarkably diminished the damage to cell migration ability, recovered the declined levels of the vasodilator factor nitric oxide (NO), elevated the expression level of endothelial nitric oxide synthases (eNOS), and inhibited the upregulated expression of vasoconstrictor factor endothelin-1 (ET-1). Moreover, α-LA pretreatment inhibited reactive oxygen species (ROS) generation, suppressed the damage to the mitochondrial membrane potential (ΔΨm) and mitigated the inhibition of adenosine triphosphate (ATP) production in HMEC-1 cells. These results suggested that α-LA could alleviate PQ-induced endothelial dysfunction by suppressing oxidative stress. In summary, our present study provides novel insight into the protective effects and pharmacological potential of α-LA against PQ toxicity in microvascular endothelial cells.

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