Activation of liver X receptor-alpha reduces activation of the renal and cardiac renin-angiotensin-aldosterone system

Irma Kuipers, Pim van der Harst, Folkert Kuipers, Linda van Genne, Maaike Goris, Jukka Y. Lehtonen, Dirk J. van Veldhuisen, Wiek H. van Gilst, Rudolf A. de Boer*

*Bijbehorende auteur voor dit werk

OnderzoeksoutputAcademicpeer review

32 Citaten (Scopus)

Samenvatting

Liver X receptor (LXR)-alpha is a pivotal player in reverse cholesterol metabolism. Recently, LXR-alpha was implicated as an immediate regulator of renin expression in a cAMP-responsive manner. To determine whether long-term LXR-alpha activation affects activation of the renal and cardiac renin-angiotensin-aldosterone system (RAAS), we treated mice with T0901317 (T09, a specific synthetic LXR agonist) in combination with the RAAS inducer isoproterenol (ISO). LXR-alpha-deficient (LXR-alpha(-/-)) and wild-type (WT) C57Bl/6J mice were treated with ISO, T09 or both for 7 days. Low-dose ISO treatment, not associated with an increase in blood pressure, caused an increase in renal renin mRNA, renin protein and ACE protein in WT mice. WT mice treated with both ISO and T09 had decreased renal renin, ACE and AT(1)R mRNA expression compared with mice treated with ISO only. Cardiac ACE mRNA expression was also reduced in the hearts of WT mice treated with ISO and T09 compared with those treated with ISO alone. The transcriptional changes of renin, ACE and AT(1)R were mostly absent in mice deficient for LXR-alpha, suggesting that these effects are importantly conferred through LXR-alpha. In conclusion, LXR-alpha activation blunts ISO-induced increases in mRNA expression of renin, AT(1)R and ACE in the heart and kidney. These findings suggest a role for LXR-alpha in RAAS regulation. Laboratory Investigation (2010) 90, 630-636; doi: 10.1038/labinvest.2010.7; published online 1 February 2010

Originele taal-2English
Pagina's (van-tot)630-636
Aantal pagina's7
TijdschriftLaboratory Investigation
Volume90
Nummer van het tijdschrift4
DOI's
StatusPublished - apr-2010

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