Department of Cardiovascular Surgery, The Second Xiangya Hospital of Central South University, Changsha, China.
Faculty of Laboratory Medicine, Xiangya Medical College, Central South University, Changsha, China.
Sci Rep. 2017 Jul 21;7(1):6169. doi: 10.1038/s41598-017-04640-6.
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.
NF-κB 调控的炎症因子在 PAH 和心肌肥厚中发挥重要作用。LXR 的激活可能通过抑制炎症途径抑制心肌肥厚；但尚不清楚 LXR 是否也参与 PAH 诱导的心肌肥厚或重构。为了进一步探讨 LXR 在 PAH 诱导的心肌肥厚和重构中的保护作用，建立了 PAH 模型，并使用 LXR 的激动剂 T0901317 来检测 LXR 激活的作用。PAH 大鼠的右心室明显出现心肌肥厚和重构，但用 T0901317 治疗的 PAH 大鼠的心肌肥厚和重构明显改善。通过 RT-PCR、Western blot 和 ELISA 检测，与 DMSO 处理的 PAH 大鼠相比，T0901317 处理的 PAH 大鼠的 NF-κB、IL-6、TNF-α 和 iNOS 显著降低。PAH 大鼠的细胞凋亡也明显减少。因此，LXR 的激活可能通过抑制 NF-κB 介导的炎症途径抑制 PAH 诱导的心肌肥厚和重构。
