Local endothelial DNA repair deficiency causes aging-resembling endothelial-specific dysfunction

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378050%3A_____%2F20%3A00525651" target="_blank" >RIV/68378050:_____/20:00525651 - isvavai.cz</a>

Result on the web

<a href="https://portlandpress.com/clinsci/article/134/7/727/222439/Local-endothelial-DNA-repair-deficiency-causes" target="_blank" >https://portlandpress.com/clinsci/article/134/7/727/222439/Local-endothelial-DNA-repair-deficiency-causes</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1042/CS20190124" target="_blank" >10.1042/CS20190124</a>

Result language

angličtina

Original language name

Local endothelial DNA repair deficiency causes aging-resembling endothelial-specific dysfunction

Original language description

We previously identified genomic instability as a causative factor for vascular aging. In the present study, we determined which vascular aging outcomes are due to local endothelial DNA damage, which was accomplished by genetic removal of ERCC1 (excision repair cross-complementation group 1) DNA repair in mice (EC-knockout (EC-KO) mice). EC-KO showed a progressive decrease in microvascular dilation of the skin, increased microvascular leakage in the kidney, decreased lung perfusion, and increased aortic stiffness compared with wild-type (WT). EC-KO showed expression of DNA damage and potential senescence marker p21 exclusively in the endothelium, as demonstrated in aorta. Also the kidney showed p21-positive cells. Vasodilator responses measured in organ baths were decreased in aorta, iliac and coronary artery EC-KO compared with WT, of which coronary artery was the earliest to be affected. Nitric oxide-mediated endothelium-dependent vasodilation was abolished in aorta and coronary artery, whereas endothelium-derived hyperpolarization and responses to exogenous nitric oxide (NO) were intact. EC-KO showed increased superoxide production compared with WT, as measured in lung tissue, rich in endothelial cells (ECs). Arterial systolic blood pressure (BP) was increased at 3 months, but normal at 5 months, at which age cardiac output (CO) was decreased. Since no further signs of cardiac dysfunction were detected, this decrease might be an adaptation to prevent an increase in BR In summary, a selective DNA repair defect in the endothelium produces features of age-related endothelial dysfunction, largely attributed to loss of endothelium-derived NO. Increased superoxide generation might contribute to the observed changes affecting end organ perfusion, as demonstrated in kidney and lung.

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

10603 - Genetics and heredity (medical genetics to be 3)

Project

<a href="/en/project/LM2015040" target="_blank" >LM2015040: Czech Centre for Phenogenomics</a><br>

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2020

Confidentiality

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

Name of the periodical

Clinical science

ISSN

0143-5221

e-ISSN

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Volume of the periodical

134

Issue of the periodical within the volume

7

Country of publishing house

GB - UNITED KINGDOM

Number of pages

20

Pages from-to

727-746

UT code for WoS article

000528253500004

EID of the result in the Scopus database

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