[Role of liver X receptors on cardiomyocyte hypertrophy].
OBJECTIVE
To investigate the expression of liver X receptors (LXR) in hypertrophic myocardium and the effect of LXR agonist T0901317 on angiotensin II (AngII) induced cardiomyocyte hypertrophy.


METHODS
Transverse aortic coarctation (TAC) or sham operation were performed in 2-month-old wide type mice (C57/B6). Two weeks later, the expression of LXR in myocardium was detected by quantitative real-time PCR analysis and Western blot analysis. The effect of LXR agonist T0901317 on AngII-induced hypertrophy in cultured neonatal rat cardiomyocytes was also assessed.


RESULTS
Quantitative real-time PCR analysis and Western blot analysis showed that LXRalpha but not LXRbeta expression was upregulated post TAC both at mRNA and protein levels (All P < 0.05). AngII induced increased [(3)H] leucine incorporation and cardiomyocyte hypertrophy were significantly reduced by T0901317 in a dose-dependent manner (P < 0.05). T0901317 also dose-dependently inhibited atrial natriuretic peptide (ANP) gene expression in cardiomyocytes (P < 0.05).


CONCLUSIONS
Our findings strongly suggest that LXR is a potent mediator of cardiomyocyte hypertrophy and LXR activation could attenuate AngII induced cardiomyocyte hypertrophy in vitro.
Yin
Ran
R
Department of Cardiology, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China.
Wang
Meng-hong
MH
Wei
Yun-feng
YF
Li
Yu-quan
YQ
Dong
Yu-gang
YG
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D000835:Animals, Wild; D002478:Cells, Cultured; D006845:Hydrocarbons, Fluorinated / Q000494:pharmacology*; D000071518:Liver X Receptors; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000473:pathology*; D057093:Orphan Nuclear Receptors / Q000819:agonists* / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology*; D005466:Fluorocarbons; D000096926:Benzenesulfonamides
D000804:Angiotensin II; D006845:Hydrocarbons, Fluorinated; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D013449:Sulfonamides; C000605214:Nr1h3 protein, mouse; C000605215:Nr1h3 protein, rat; C423915:T0901317; D005466:Fluorocarbons; D000096926:Benzenesulfonamides