Počet záznamů: 1
Downregulation of Plzf Gene Ameliorates Metabolic and Cardiac Traits in the Spontaneously Hypertensive Rat
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SYSNO ASEP 0474947 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název Downregulation of Plzf Gene Ameliorates Metabolic and Cardiac Traits in the Spontaneously Hypertensive Rat Tvůrce(i) Liška, F. (CZ)
Landa, Vladimír (FGU-C) RID
Zídek, Václav (FGU-C) RID
Mlejnek, Petr (FGU-C) RID, ORCID
Šilhavý, Jan (FGU-C) RID, ORCID
Šimáková, Miroslava (FGU-C) RID, ORCID
Strnad, Hynek (UMG-J) RID
Trnovská, J. (CZ)
Škop, V. (CZ)
Kazdová, L. (CZ)
Starker, C.G. (US)
Voytas, D.F. (US)
Izsvák, Z. (DE)
Mancini, M. (IT)
Šeda, O. (CZ)
Křen, V. (CZ)
Pravenec, Michal (FGU-C) RID, ORCIDZdroj.dok. Hypertension. - : Lippincott Williams & Wilkins - ISSN 0194-911X
Roč. 69, č. 6 (2017), s. 1084-1091Poč.str. 8 s. Jazyk dok. eng - angličtina Země vyd. US - Spojené státy americké Klíč. slova fibrosis ; hypertension ; hypertrophy ; left ventricular rats ; inbred ; SHR ; transcriptome Vědní obor RIV EB - Genetika a molekulární biologie Obor OECD Cardiac and Cardiovascular systems Vědní obor RIV – spolupráce Ústav molekulární genetiky - Genetika a molekulární biologie CEP GB14-36804G GA ČR - Grantová agentura ČR LL1204 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy Institucionální podpora FGU-C - RVO:67985823 ; UMG-J - RVO:68378050 UT WOS 000400993600069 EID SCOPUS 85017450596 DOI 10.1161/HYPERTENSIONAHA.116.08798 Anotace 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. Pracoviště Fyziologický ústav Kontakt Lucie Trajhanová, lucie.trajhanova@fgu.cas.cz, Tel.: 241 062 400 Rok sběru 2018
Počet záznamů: 1