Neutrophil Elastase Promotes Neointimal Hyperplasia by Targeting TLR4‐NFкB Signalling

2021 ◽  
Author(s):  
Mei Yang ◽  
Qishan Chen ◽  
Li Mei ◽  
Guanmei Wen ◽  
Weiwei An ◽  
...  
Keyword(s):  
Neutrophil Elastase ◽  
Neointimal Hyperplasia

Neutrophil Elastase Potentiates Cathepsin G-lnduced Platelet Activation

1992 ◽  
Vol 68 (05) ◽  
pp. 570-576 ◽  
Author(s):  
Mary A Selak
Keyword(s):  
Neutrophil Elastase ◽  
Cell Activation ◽  
Thromboxane A2 ◽  
Creatine Phosphate ◽  
Dense Granule ◽  
Cathepsin G ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Low Concentrations ◽  
High Concentrations

SummaryWe have previously demonstrated that human neutrophil cathepsin G is a strong platelet agonist that binds to a specific receptor. This work describes the effect of neutrophil elastase on cathepsin G-induced platelet responses. While platelets were not activated by high concentrations of neutrophil elastase by itself, elastase enhanced aggregation, secretion and calcium mobilization induced by low concentrations of cathepsin G. Platelet aggregation and secretion were potentiated in a concentration-dependent manner by neutrophil elastase with maximal responses observable at 200 nM. Enhancement was observed when elastase was preincubated with platelets for time intervals of 10–60 s prior to addition of a low concentration of cathepsin G and required catalytically-active elastase since phenylmethanesulphonyl fluoride-inhibited enzyme failed to potentiate cell activation. Neutrophil elastase potentiation of platelet responses induced by low concentrations of cathepsin G was markedly inhibited by creatine phosphate/creatine phosphokinase and/or indomethacin, indicating that the synergism between elastase and cathepsin G required the participation of ADP and thromboxane A2. On the other hand, platelet responses were not attenuated by the PAF antagonist BN 52021, signifying that PAF-acether did not play a role in elastase potentiation. At higher concentrations porcine pancreatic elastase exhibits similar effects to neutrophil elastase, demonstrating that the effect of elastase was not unique to the neutrophil protease. While neutrophil elastase failed to alter the ability of cathepsin G to hydrolyze a synthetic chromogenic substrate, preincubation of platelets with elastase increased the apparent affinity of cathepsin G binding to platelets. In contrast to their effect on cathepsin G-induced platelet responses, neither neutrophil nor pancreatic elasatse potentiated aggregation or dense granule release initiated by ADP, PAF-acether, arachidonic acid or U46619, a thromboxane A2 mimetic. Moreover, unlike its effect on cathepsin G, neutrophil elastase inhibited thrombin-induced responses. The current observations demonstrate that elastase can potentiate platelet responses mediated by low concentrations of cathepsin G, suggesting that both enzymes may function synergistically to activate platelets under conditions where neutrophil degranulation occurs.

Inhibition of Leucocyte and Platelet Adhesion Reduces Neointimal Hyperplasia after Arterial Injury

1997 ◽  
Vol 77 (04) ◽  
pp. 783-788 ◽  
Author(s):  
Paolo Golino ◽  
Giuseppe Ambrosio ◽  
Massimo Ragni ◽  
Plinio Cirillo ◽  
Nicolino Esposito ◽  
...  
Keyword(s):  
Coronary Angioplasty ◽  
Neointimal Hyperplasia ◽  
Rabbit Model ◽  
Arterial Injury ◽  
Platelet Glycoprotein ◽  
Beneficial Effects ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Factor Interaction ◽  
Adhesion Complex

SummaryRestenosis following coronary angioplasty is thought to result from migration and proliferation of medial smooth muscle cells. However, the factors that initiate this proliferation are still unknown. In a rabbit model of carotid artery injury, we tested the hypothesis that activated platelets and leucocytes might contribute to the development of neointimal hyperplasia. Following arterial injury, rabbits received either no treatment, R15.7, a monoclonal antibody against the leucocyte CD ll/CD 18 adhesion complex, aurintricarboxylic acid (ATA), a sub stance that inhibits platelet glycoprotein Ib-von Willebrand factor interaction, or the combination of R15.7 and ATA. After 21 days, the extent of neointimal hyperplasia was evaluated by planimetry on histological arterial sections. The area of neointima averaged 0.51 ±0.07 mm2 in control animals and it was significantly reduced by administrationof either R15.7 or ATA alone to 0.12 ± 0.05 and 0.20 ±0.01 mm2, respectively (p <0.05 vs controls for both groups). The animals that received the combination of R15.7 and ATA showed a further reduction in neointimal hyperplasia, as compared to animals that received ATA alone (p <0.05 vs ATA alone). These data indicate that platelets and leucocytes play animportant role in the pathophysi ology of neointimal hyperplasia in this experimental model. Interven tions that reduce platelet and leucocyte adhesion to vessel wall might have beneficial effects in reducing restenosis following coronary angioplasty.

Neutrophil Elastase Contributes to the Early Molecular Abnormalities of the Retina in Diabetes

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 590-P
Author(s):  
HAITAO LIU ◽  
TIMOTHY KERN
Keyword(s):  
Neutrophil Elastase ◽  
Molecular Abnormalities

Continuous Subcutaneous Angiopeptin Treatment Significantly Reduces Neointimal Hyperplasia in a Porcine Coronary In-Stent Restenosis Model

Circulation ◽  
1997 ◽  
Vol 95 (2) ◽  
pp. 449-454 ◽  
Author(s):  
Mun K. Hong ◽  
Kenneth M. Kent ◽  
Roxana Mehran ◽  
Gary S. Mintz ◽  
Fermin O. Tio ◽  
...  
Keyword(s):  
Neointimal Hyperplasia ◽  
Stent Restenosis ◽  
In Stent Restenosis

Neutrophil elastase and obliterative bronchiolitis

1994 ◽  
Vol 7 (s1) ◽  
pp. 402-403 ◽  
Author(s):  
J.P. Scott ◽  
D.W. Holt ◽  
J. Wallwork
Keyword(s):  
Neutrophil Elastase ◽  
Obliterative Bronchiolitis
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