Activation of LXRα improves cardiac remodeling induced by pulmonary artery hypertension in rats.

Abstract

Inflammatory factors regulated by NF-κB play a significant role in PAH and myocardial hypertrophy. LXR activation may inhibit myocardial hypertrophy via suppressing inflammatory pathways; it is unknown whether LXR is also involved in PAH-induced myocardial hypertrophy or remodeling. To further explore the protective effect of LXR in PAH-induced cardiac hypertrophy and remodeling, a PAH model was developed, and T0901317, an agonist of LXR, was used to examine the effect of LXR activation. PAH rats demonstrated obvious cardiac hypertrophy and remodeling in the right ventricle, but significant improvement of cardiac hypertrophy and remodeling was observed in PAH rats treated with T0901317. Through RT-PCR, Western blot and ELISA examination, NF-κB, IL-6, TNF-α, and iNOS were found to be significantly reduced in PAH rats treated with T0901317 compared to PAH rats treated with DMSO. Apoptosis was also significantly reduced in PAH rats treated with T0901317. Thus, LXR activation may inhibit PAH-induced cardiac hypertrophy and remodeling by inhibiting NF-κB-mediated inflammatory pathways.

• Authors: Yibo Gong, Yifeng Yang, Qin Wu, Ge Gao, Yin Liu, Yaoyao Xiong, Can Huang, Sijie Wu
• Journal: Scientific reports (Sci Rep) Vol. 7 Issue 1 Pg. 6169 (07 21 2017) ISSN: 2045-2322 [Electronic] England
• PMID: 28733583 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Hydrocarbons, Fluorinated
• Il6 protein, rat
• Interleukin-6
• Liver X Receptors
• NF-kappa B
• Nr1h3 protein, rat
• Sulfonamides
• T0901317
• Tumor Necrosis Factor-alpha
• Nitric Oxide Synthase Type II
• Nos2 protein, rat

Topics

• Animals
• Disease Models, Animal
• Gene Expression Regulation (drug effects)
• Humans
• Hydrocarbons, Fluorinated (administration & dosage, pharmacology)
• Hypertension, Pulmonary (complications, genetics, metabolism)
• Hypertrophy, Right Ventricular (drug therapy, genetics, metabolism)
• Interleukin-6 (genetics, metabolism)
• Liver X Receptors (metabolism)
• NF-kappa B (genetics, metabolism)
• Nitric Oxide Synthase Type II (genetics, metabolism)
• Rats
• Sulfonamides (administration & dosage, pharmacology)
• Tumor Necrosis Factor-alpha (genetics, metabolism)