Cardiovascular Research Advance Access first published online on June 1, 2009
This version [Corrected Proof] published online on June 27, 2009
Cardiovascular Research, doi:10.1093/cvr/cvp180
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Liver X receptors are negative regulators of cardiac hypertrophy via suppressing NF-
B signalling
1 Department of Nutrition Sciences, University of Alabama at Birmingham, Webb 435, 1675 University Boulevard, Birmingham, AL 35242, USA
2 Department of Cardio-Thoracic Surgery, The Second Xiangya Hospital, Central South University, Changsha, China
3 Department of Cardiology, Jiangxi Medical College, Nanchang, China
4 Cardiovascular Research Institute, Morehouse School of Medicine, Atlanta, GA, USA
* Corresponding author. Tel:+1 205 996 6022; fax: +1 205 934 7049. E-mail address: qyang{at}uab.edu
Aims: Nuclear factor-
B (NF-B) plays a critical role in cell growth and inflammation during the progression of cardiac hypertrophy and heart failure. Several members of nuclear receptor superfamily, including liver X receptors (LXR
and LXRβ), have been shown to suppress inflammatory responses, but little is known about their effects in cardiomyocytes.
Methods and results: We investigated LXR expression patterns in pressure overload-induced hypertrophic hearts and the hypertrophic growth of the LXR-deficient hearts from mice (C57/B6) in response to pressure overload. The underlying mechanisms were also explored using cultured myocytes. We found that cardiac expression of LXR was upregulated in pressure overload-induced left ventricular hypertrophy in mice. Transverse aorta coarctation-induced left ventricular hypertrophy was exacerbated in LXR-null mice relative to control mice. A synthetic LXR ligand, T1317, suppressed cardiomyocyte hypertrophy in response to angiotensin II and lipopolysaccharide treatments. In addition, LXR activation suppressed NF-B signalling and the expression of associated inflammatory factors. Overexpression of constitutively active LXR and β in cultured myocytes suppressed NF-B activity.
Conclusion: LXRs are negative regulators of cardiac growth and inflammation via suppressing NF-B signalling in cardiomyocytes. This should provide new insights into novel therapeutic targets for treating cardiac hypertrophy and heart failure.
KEYWORDS LXR; LXRβ; Cardiac hypertrophy; Inflammation; Angiotensin II; LPS; NF-B; Cardiomyocytes
Time for primary review: 24 days
The first two authors contributed equally to the study.