Bradykinin enhances in vitro procoagulant and antifibrinolytic properties of rat vascular endothelial cells

Kimura, Shinzo; Tsuji, Hajime; Nishimura, Hiromi; Kato, Hisato; Ukimura, Naoki; Yano, Shingo; Kunieda, Yasufumi; Kawano, Hidehiko; Nakagawa, Keigo; Nakagawa, Masao

doi:10.1016/s0049-3848(02)00070-1

Cited by 16 publications

(14 citation statements)

References 41 publications

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“…Kimura et al demonstrated that bradykinin increases PAI-1 mRNA and protein expression in rat vascular endothelial cells and that the effect is negatively affected by NO. 35 In contrast, Okada et al reported that bradykinin decreases PAI-1 expression in murine renal tubulointerstitial cells during ACE inhibition. 36 The finding that bradykinin B 2 receptor blockade abolished the rise in PAI-1 after hemodialysis in the study presented here suggests that in CHD patients that exhibit endothelial dysfunction, 37 the proinflammatory effects of bradykinin predominate in regulating PAI-1, at least during hemodialysis.…”

Section: Discussionmentioning

confidence: 95%

Endogenous Bradykinin Contributes to Increased Plasminogen Activator Inhibitor 1 Antigen following Hemodialysis

Marney¹,

Ma²,

Luther

et al. 2009

Journal of the American Society of Nephrology

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Oxidative stress and inflammation predict cardiovascular events in chronic hemodialysis patients. Hemodialysis activates the kallikrein-kinin system, increasing bradykinin. Bradykinin promotes inflammation but also stimulates endothelial release of tissue-plasminogen activator and inhibits platelet aggregation. Understanding the detrimental and beneficial effects of endogenous bradykinin during hemodialysis has implications for the treatment of cardiovascular disease in the hemodialysis population. To test the hypothesis that bradykinin contributes to the inflammatory and fibrinolytic responses to dialysis, we conducted a double-blind, randomized, placebo-controlled crossover study comparing the effect of the bradykinin B 2 receptor blocker HOE-140 with vehicle on markers of oxidative stress, inflammation, fibrinolysis, and coagulation in nine hemodialysis patients without coronary artery disease. Bradykinin receptor antagonism did not affect the mean arterial pressure or heart rate response to dialysis. Monocyte chemoattractant protein 1 (MCP-1) peaked postdialysis; HOE-140 blunted the increase in MCP-1 (5.9 Ϯ 5.9 versus 25.6 Ϯ 20.1 pg/ml, P ϭ 0.01). HOE-140 also abolished the increase in plasminogen activator inhibitor 1 (PAI-1) antigen observed at the end of dialysis. In contrast, HOE-140 significantly accentuated the effect of dialysis on F 2 -isoprostanes and P-selectin. Taken together, these results suggest that endogenous bradykinin contributes to increases in MCP-1 and PAI-1 antigen after hemodialysis via its B 2 receptor. Factors that increase the production of bradykinin or decrease its degradation may enhance the inflammatory response to hemodialysis.

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Section: Discussionmentioning

confidence: 95%

Endogenous Bradykinin Contributes to Increased Plasminogen Activator Inhibitor 1 Antigen following Hemodialysis

Marney¹,

Ma²,

Luther

et al. 2009

Journal of the American Society of Nephrology

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“…This protease plays a critical role both in the immune regulation and in viral replication, in that it regulates the proteolytic cleavage of polyproteins. M pro drives the cleavage of polyproteins pp1a and pp1ab, which in turn are responsible for the generation of functional proteins such as RNA polymerase, endoribonuclease and exoribonuclease (Khan et al, 2020). For this reason, it has been speculated that M pro could represent an attractive target for COVID-19 treatment.…”

Section: Biological Targets For Sars-cov-2mentioning

confidence: 99%

“…For this reason, it has been speculated that M pro could represent an attractive target for COVID-19 treatment. In this context, two different molecular docking and molecular dynamic simulation studies revealed four drugs that could act against M pro :-the antibacterial drug talampicillin, the antipsychotic drug lurasidone (Elmezayen, Al-Obaidi, Şahin, & Yelekçi, 2020) and the antiviral drug raltegravir and paritaprevir, which were already used in the antiretroviral therapy against the human immunodeficiency virus (HIV) infections, as integrase strand transfer inhibitors (INSTIs) (Khan et al, 2020). M pro also cleaves the 2 0 -O-ribose methyltransferase (2 0 -O-MTase), a protein that catalyses the methylation of 5 0 -terminal cap structure of viral mRNAs (Chen et al, 2011).…”

Section: Biological Targets For Sars-cov-2mentioning

confidence: 99%

A lesson from a saboteur: High‐MW kininogen impact in coronavirus‐induced disease 2019

Colarusso

Terlizzi

Pinto

et al. 2020

British J Pharmacology

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The newly identified coronavirus SARS-CoV-2 that spread from China is causing the pandemic COVID-19 with a fatality rate from 5-15%. It causes fever, cough, myalgia, fatigue up to dyspnoea, responsible for hospitalization and artificial oxygenation. SARS-CoV-2 infects human cells using ACE2, the transmembrane protease serine 2 (TMPRSS2) and the SARS-CoV-2 main protease (M pro). Once bound to ACE2 and the other two proteases in concert they allow the virus replication and spread throughout the body. Our attention has been focused on the role of ACE2 as its binding to by the virus increases bradykinin and its metabolites, which facilitate inflammation in the lung (causing cough and fever), coagulation and the complement system. These three systems are involved in angioedema, cardiovascular dysfunction and sepsis, pathologies which occur in COVID-19 patients. Thus, we propose that blocking the kallikrein-kinin system with lanadelumab, approved for hereditary angioedema, will prevent facilitation of these 3 systems.

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“…An increase in AT2R may lead angiotensin to favor this receptor over AT1R and cause an elevation of NO and prostacyclin levels[78]. Studies looking at rat models that express both BK receptors show, in vitro, that BK acting through the B2 receptor on the surface of endothelial cells promotes the expression of procoagulant and antifybrinolytic proteins, such as tissue factor (TF) and plasminogen activator inhibitor 1 (PAI-1)[79]. This effect translated well to the human model described in the study using a selective bradykinin B2 receptor antagonist, which demonstrated that inhibition of BK activity on the B2 receptor resulted in a decrease in vasodilatation and t-PA release, which may cause a decrease in fibrinolytic activity[79–81].…”

Section: Kks Functionmentioning

confidence: 99%

Human Plasma Kallikrein-Kinin System: Physiological and Biochemical Parameters

Bryant

Shariat‐Madar²

2009

CHAMC

118

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The plasma kallikrein-kinin system (KKS) plays a critical role in human physiology. The KKS encompasses coagulation factor XII (FXII), the complex of prekallikrein (PK) and high molecular weight kininogen (HK). The conversion of plasma to kallikrein by the activated FXII and in response to numerous different stimuli leads to the generation of bradykinin (BK) and activated HK (HKa, an antiangiogenic peptide). BK is a proinflammatory peptide, a pain mediator and potent vasodilator, leading to robust accumulation of fluid in the interstitium. Systemic production of BK, HKa with the interplay between BK bound-BK receptors and the soluble form of HKa are key to angiogenesis and hemodynamics. KKS has been implicated in the pathogenesis of inflammation, hypertension, endotoxemia, and coagulopathy. In all these cases increased BK levels is the hallmark. In some cases, the persistent production of BK due to the deficiency of the blood protein C1-inhibitor, which controls FXII, is detrimental to the survival of the patients with hereditary angioedema (HAE). In others, the inability of angiotensin converting enzyme (ACE) to degrade BK leads to elevated BK levels and edema in patients on ACE inhibitors. Thus, the mechanisms that interfere with BK liberation or degradation would lead to blood pressure dysfunction. In contrast, anti-kallikrein treatment could have adverse effects in hemodynamic changes induced by vasoconstrictor agents. Genetic models of kallikrein deficiency are needed to evaluate the quantitative role of kallikrein and to validate whether strategies designed to activate or inhibit kallikrein may be important for regulating whole-body BK sensitivity.

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Bradykinin enhances in vitro procoagulant and antifibrinolytic properties of rat vascular endothelial cells

Cited by 16 publications

References 41 publications

Endogenous Bradykinin Contributes to Increased Plasminogen Activator Inhibitor 1 Antigen following Hemodialysis

Endogenous Bradykinin Contributes to Increased Plasminogen Activator Inhibitor 1 Antigen following Hemodialysis

A lesson from a saboteur: High‐MW kininogen impact in coronavirus‐induced disease 2019

Human Plasma Kallikrein-Kinin System: Physiological and Biochemical Parameters

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