Myeloperoxidase aggravates pulmonary arterial hypertension by activation of vascular Rho-kinase

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00159816%3A_____%2F18%3A00068688" target="_blank" >RIV/00159816:_____/18:00068688 - isvavai.cz</a>

Alternative codes found

RIV/68081707:_____/18:00491102

Result on the web

<a href="https://df6sxcketz7bb.cloudfront.net/manuscripts/97000/97530/jci.insight.97530.v1.pdf" target="_blank" >https://df6sxcketz7bb.cloudfront.net/manuscripts/97000/97530/jci.insight.97530.v1.pdf</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1172/jci.insight.97530" target="_blank" >10.1172/jci.insight.97530</a>

Result language

angličtina

Original language name

Myeloperoxidase aggravates pulmonary arterial hypertension by activation of vascular Rho-kinase

Original language description

Pulmonary arterial hypertension (PAH) remains a disease with limited therapeutic options and dismal prognosis. Despite its etiologic heterogeneity, the underlying unifying pathophysiology is characterized by increased vascular tone and adverse remodeling of the pulmonary circulation. Myeloperoxidase (MPO), an enzyme abundantly expressed in neutrophils, has potent vasoconstrictive and profibrotic properties, thus qualifying as a potential contributor to this disease. Here, we sought to investigate whether MPO is causally linked to the pathophysiology of PAH. Investigation of 2 independent clinical cohorts revealed that MPO plasma levels were elevated in subjects with PAH and predicted adverse outcome. Experimental analyses showed that, upon hypoxia, right ventricular pressure was less increased in Mpo(-/-) than in WT mice. The hypoxia-induced activation of the Rho-kinase pathway, a critical subcellular signaling pathway yielding vasoconstriction and structural vascular remodeling, was blunted in Mpo(-/-) mice. Mice subjected to i.v. infusion of MPO revealed activation of Rho-kinase and increased right ventricular pressure, which was prevented by coinfusion of the Rho-kinase inhibitor Y-27632. In the Sugen5416/hypoxia rat model, PAH was attenuated by the MPO inhibitor AZM198. The current data demonstrate a tight mechanistic link between MPO, the activation of Rho-kinase, and adverse pulmonary vascular function, thus pointing toward a potentially novel avenue of treatment.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

30100 - Basic medicine

Project

<a href="/en/project/LQ1605" target="_blank" >LQ1605: Translational Medicine</a><br>

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2018

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

JCI INSIGHT

ISSN

2379-3708

e-ISSN

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Volume of the periodical

3

Issue of the periodical within the volume

11

Country of publishing house

US - UNITED STATES

Number of pages

17

Pages from-to

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UT code for WoS article

000434866600004

EID of the result in the Scopus database

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