Downregulation of Plzf Gene Ameliorates Metabolic and Cardiac Traits in the Spontaneously Hypertensive Rat
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F67985823%3A_____%2F17%3A00474947" target="_blank" >RIV/67985823:_____/17:00474947 - isvavai.cz</a>
Alternative codes found
RIV/68378050:_____/17:00474947 RIV/00216208:11110/17:10363897
Result on the web
<a href="http://dx.doi.org/10.1161/HYPERTENSIONAHA.116.08798" target="_blank" >http://dx.doi.org/10.1161/HYPERTENSIONAHA.116.08798</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1161/HYPERTENSIONAHA.116.08798" target="_blank" >10.1161/HYPERTENSIONAHA.116.08798</a>
Alternative languages
Result language
angličtina
Original language name
Downregulation of Plzf Gene Ameliorates Metabolic and Cardiac Traits in the Spontaneously Hypertensive Rat
Original language description
The spontaneously hypertensive rat (SHR), one of the most widely used model of essential hypertension, is predisposed to left ventricular hypertrophy, myocardial fibrosis, and metabolic disturbances. Recently, quantitative trait loci influencing blood pressure, left ventricular mass, and heart interstitial fibrosis were genetically isolated within a minimal congenic subline that contains only 7 genes, including mutant Plzf (promyelocytic leukemia zinc finger) candidate gene. To identify Plzf as a quantitative trait gene, we targeted Plzf in the SHR using the transcription activator-like effector nuclease technique and obtained SHR line harboring targeted Plzf gene with a premature stop codon. Because the Plzf targeted allele is semilethal, morphologically normal heterozygous rats were used for metabolic and hemodynamic analyses. SHR-Plzf(+/-) heterozygotes versus SHR wild-type controls exhibited reduced body weight and relative weight of epididymal fat, lower serum and liver triglycerides and cholesterol, and better glucose tolerance. In addition, SHR-Plzf(+/-) rats exhibited significantly increased sensitivity of adipose and muscle tissue to insulin action when compared with wild-type controls. Blood pressure was comparable in SHR versus SHR-Plzf(+/-), however, there was significant amelioration of cardiomyocyte hypertrophy and cardiac fibrosis in SHR-Plzf(+/-) rats. Gene expression profiles in the liver and expression of selected genes in the heart revealed differentially expressed genes that play a role in metabolic pathways, PPAR (peroxisome proliferator-activated receptor) signaling, and cell cycle regulation. These results provide evidence for an important role of Plzf in regulation of metabolic and cardiac traits in the rat and suggest a cross talk between cell cycle regulators, metabolism, cardiac hypertrophy, and fibrosis.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30201 - Cardiac and Cardiovascular systems
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2017
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Hypertension
ISSN
0194-911X
e-ISSN
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Volume of the periodical
69
Issue of the periodical within the volume
6
Country of publishing house
US - UNITED STATES
Number of pages
8
Pages from-to
1084-1091
UT code for WoS article
000400993600069
EID of the result in the Scopus database
2-s2.0-85017450596