Nafamostat mesilate promotes endothelium-dependent vasorelaxation via the Akt-eNOS dependent pathway

Choi, Si Hwan; Kwon, Hyon-Jo; Song, Hee‐Jung; Choi, Si Wan; Nagar, Harsha; Piao, Shuyu; Jung, Sungyup; Jeon, Byeong Hwa; Kim, Dong Ho; Kim, Cuk-Seong

doi:10.4196/kjpp.2016.20.5.539

Cited by 11 publications

(5 citation statements)

References 24 publications

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“…Consistent with these studies, upregulated p-eNOS/NO expression was observed in FIR radiation-treated endothelial cells compared with control cells (Figures 1 and 3). In addition, our previous studies reported that Akt is involved in eNOS activation and induced NO production under different experimental conditions [25, 26]. In the present study, we found that FIR treatment significantly stimulated Akt/eNOS phosphorylation (Figures 1 and 3), which may be one of the upstream pathways for NO production.…”

Section: Discussionsupporting

confidence: 72%

Far-Infrared-Emitting Sericite Board Upregulates Endothelial Nitric Oxide Synthase Activity through Increasing Biosynthesis of Tetrahydrobiopterin in Endothelial Cells

Kim

Lee

Song

et al. 2019

Evidence-Based Complementary and Alternative Medicine

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Far-infrared ray (FIR) therapy has been reported to exert beneficial effects on cardiovascular function by elevating endothelial nitric oxide synthesis (eNOS) activity and nitric oxide (NO) production. Tetrahydrobiopterin (BH4) is a key determinant of eNOS-dependent NO synthesis in vascular endothelial cells. However, whether BH4 synthesis is associated with the effects of FIR on eNOS/NO production has not yet been investigated. In this study, we investigated the effects of FIR on BH4-dependent eNOS/NO production and vascular function. We used FIR-emitting sericite boards as an experimental material and placed human umbilical vein endothelial cells (HUVECs) and Sprague–Dawley rats on the boards with or without FIR irradiation and then evaluated vascular relaxation by detecting NO generation, BH4 synthesis, and Akt/eNOS activation. Our results showed that FIR radiation significantly enhanced Akt/eNOS phosphorylation and NO production in human endothelial cells and aorta tissues. FIR can also induce BH4 storage by elevating levels of enzymes (e.g., guanosine triphosphate cyclohydrolase-1, 6-pyruvoyl tetrahydrobiopterin synthase, sepiapterin reductase, and dihydrofolate reductase), which ultimately results in NO production. These results indicate that FIR upregulated eNOS-dependent NO generation via BH4 synthesis and Akt phosphorylation, which contributes to the regulation of vascular function. This might develop potential clinical application of FIR to treat vascular diseases by augmenting the BH4/NO pathway.

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Section: Discussionsupporting

confidence: 72%

Far-Infrared-Emitting Sericite Board Upregulates Endothelial Nitric Oxide Synthase Activity through Increasing Biosynthesis of Tetrahydrobiopterin in Endothelial Cells

Kim

Lee

Song

et al. 2019

Evidence-Based Complementary and Alternative Medicine

Self Cite

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“…Endothelial nitric oxide synthase (eNOS), one of the three NOS isoforms (the other two isoforms are inducible NOS (iNOS), and neuronal NOS (nNOS)), is the key enzyme responsible for NO production in blood vessels. eNOS activity increases NO synthesis in HUVECs [29,30] and is activated by direct phosphorylation of Akt [31]. The Akt/eNOS pathway regulates the production of NO.…”

Section: Antihypertensive Activity Of Peptides Via the Akt/enos Pathwaymentioning

confidence: 99%

Anti-Hypertensive Activity of Novel Peptides Identified from Olive Flounder (Paralichthys olivaceus) Surimi

Lee

et al. 2020

Foods

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There is a growing interest in the health benefits of functional foods. A benefit that has been long sought is the control of hypertension through dietary approaches. Hypertension has been implicated as a risk factor for cardiovascular disease and is therefore of clinical significance. Here, we aim to demonstrate the antihypertensive activity of novel peptides derived from surimi, a functional food ingredient made from refined fish myofibrillar proteins. Three peptides, Ile-Val-Asp-Arg (IVDR), Trp-Tyr-Lys (WYK), and Val-Ala-Ser-Val-Ile (VASVI), were isolated from surimi made from the olive flounder (Paralichthys olivaceus). Our results show that IVDR, WYK, and VASVI exhibited high Angiotensin I-converting Enzyme (ACE) inhibition activity. These peptides are also shown to increase phosphorylation of protein kinase B (Akt) and endothelial nitric oxide synthase (eNOS), and significantly promote nitric oxide (NO) production in human umbilical vein endothelial cells. Oral administration of the peptides decreased blood pressure in spontaneously hypertensive rats (SHRs), thereby confirming that the peptides derived from surimi perform antihypertensive activity via the Akt/eNOS pathway. These results indicate that surimi made from P. olivaceus contains novel antihypertensive peptides that could be used to enhance the health benefits of food ingredients.

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“…Beyond their anticoagulant propriety, both Gabexate and Nafamostat mesylate show anti-inflammatory effects, which could be useful in COVID-19 uncontrolled inflammation (Tay et al 2020). In particular, Gabexate mesylate decreases the production of inflammatory cytokines, such as TNF-α by attenuating NF-κB and JNK pathway activity, most probably through the proteolytic destruction of IκB (Yuksel et al 2003); Nafamostat mesylate shows an anti-inflammatory effectin vitro , where it mediates the inhibition of lipopolysaccharide-induced nitric oxide production, apoptosis, IL-6 and IL-8 production in cell cultures (Kang et al 2015;Choi et al 2016). In this context, Camostat mesylate could be also useful to reduce the production of inflammatory cytokines due to SARS-CoV2 infection.…”

Section: Approaching Therapies For Covid-19 Patientsmentioning

confidence: 99%

A lesson from an old friend: high molecular weight kininogen (HMWK) impact in COVID-19.

Colarusso

Terlizzi

Pinto

et al. 2020

Preprint

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) is a newly identified coronavirus which has spread from China to the rest of the world causing the pandemic coronavirus disease 19 . It has fatality rate that floats from 5 to 15% and the symtoms are fever, cough, myalgia and/or fatigue up to dyspnea, responsible for hospitalization and in most of the cases of artificial oxygenation. In the attempt to understand how the virus spreads and how to pharmacologically abolish it, it was highlighted that SARS-CoV2 infects human cells by means of angiotensin converting enzyme 2 (ACE2), transmembrane protease serine 2 (TMPRSS2) and 3-chymotrypsin-like protease (3CLpro), also known as Mpro. Once bound to its receptor ACE2, the other two proteases, in concert with the receptor-mediated signaling, allow virus replication and spread throughout the body. Our attention has been focused on the role of ACE2 in that its blockade by the virus increases Bradykinin and its metabolites, well known to facilitate inflammation in the lung (responsible for cough and fever), facilitate both the coagulation and complement system, three mechanisms that are typical of angioedema, cardiovascular dysfunction and sepsis, pathologies which symptoms occur in COVID-19 patients. Thus, we propose to pharmacologically block the kallicrein-kinin system upstream bradykinin and the ensuing inflammation, coagulation and complement activation by means of lanadelumab, which is a clinically approved drug for hereditary angioedema.

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Nafamostat mesilate promotes endothelium-dependent vasorelaxation via the Akt-eNOS dependent pathway

Cited by 11 publications

References 24 publications

Far-Infrared-Emitting Sericite Board Upregulates Endothelial Nitric Oxide Synthase Activity through Increasing Biosynthesis of Tetrahydrobiopterin in Endothelial Cells

Far-Infrared-Emitting Sericite Board Upregulates Endothelial Nitric Oxide Synthase Activity through Increasing Biosynthesis of Tetrahydrobiopterin in Endothelial Cells

Anti-Hypertensive Activity of Novel Peptides Identified from Olive Flounder (Paralichthys olivaceus) Surimi

A lesson from an old friend: high molecular weight kininogen (HMWK) impact in COVID-19.

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