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Activation of liver X receptors with T0901317 attenuates cardiac hypertrophy in vivo
Author(s) -
Kuipers Irma,
Li Jiang,
VreeswijkBaudoin Inge,
Koster Johan,
Harst Pim,
Silljé Herman H.W.,
Kuipers Folkert,
Veldhuisen Dirk J.,
Gilst Wiek H.,
Boer Rudolf A.
Publication year - 2010
Publication title -
european journal of heart failure
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.149
H-Index - 133
eISSN - 1879-0844
pISSN - 1388-9842
DOI - 10.1093/eurjhf/hfq109
Subject(s) - liver x receptor , medicine , endocrinology , abcg1 , agonist , in vivo , muscle hypertrophy , abca1 , pressure overload , receptor , nuclear receptor , biology , cardiac hypertrophy , transcription factor , transporter , biochemistry , microbiology and biotechnology , gene
Aims Liver X receptor (LXR) is a nuclear receptor regulating cholesterol metabolism. Liver X receptor has also been shown to exert anti‐proliferative and anti‐inflammatory properties. In this study, we evaluated the effect of LXR activation on cardiac hypertrophy in vitro and in vivo . Methods and results Treatment with the synthetic LXR agonist T0901317 (T09) attenuated the hypertrophic response of cultured cardiomyocytes to endothelin‐1 almost to control levels. siRNA interference showed that this effect was indeed LXR specific. To corroborate these findings in vivo , abdominal aortic constriction (AC) was used as a pressure overload model to induce cardiac hypertrophy in wild‐type and LXR‐α‐deficient (LXR‐α −/− ) mice. In wild‐type mice, T09 treatment resulted in a decrease of cardiac wall thickening 4 and 7 weeks after AC. Also, after 7 weeks of AC, mean arterial blood pressure and left ventricular weight/body weight (LVW/BW) ratios were decreased in T09 treated mice. These effects were not observed in LXR‐α −/− mice, indicating that the beneficial effect of LXR activation on cardiac hypertrophy is attributable to the LXR‐α isoform. T09 induced robust cardiac expression of metabolic genes which are downstream of LXR‐α, such as SREBP‐1c, ABCA1, and ABCG1. Conclusion Together these results indicate that LXR exerts salutary effects in cardiac hypertrophy, possibly via metabolic remodelling.