Department of Endocrinology, Shandong Provincial Hospital affiliated to Shandong University, Shandong Key Laboratory of Endocrinology and Lipid Metabolism, Institute of Endocrinology and Metabolism, Shandong Academy of Clinical Medicine, Jinan, Shandong, China.
Scientific Center, Shandong Provincial Hospital affiliated to Shandong University, Jinan, Shandong, China.
J Exp Med. 2019 May 6;216(5):1182-1198. doi: 10.1084/jem.20181473. Epub 2019 Apr 2.
Subclinical hypothyroidism is associated with cardiovascular diseases, yet the underlying mechanism remains largely unknown. Herein, in a common population ( = 1,103), TSH level was found to be independently correlated with both carotid plaque prevalence and intima-media thickness. Consistently, TSH receptor ablation in mice attenuated atherogenesis, accompanied by decreased vascular inflammation and macrophage burden in atherosclerotic plaques. These results were also observed in myeloid-specific -deficient mice, which indicated macrophages to be a critical target of the proinflammatory and atherogenic effects of TSH. In vitro experiments further revealed that TSH activated MAPKs (ERK1/2, p38α, and JNK) and IκB/p65 pathways in macrophages and increased inflammatory cytokine production and their recruitment of monocytes. Thus, the present study has elucidated the new mechanisms by which TSH, as an independent risk factor of atherosclerosis, aggravates vascular inflammation and contributes to atherogenesis.
亚临床甲状腺功能减退症与心血管疾病相关，但潜在机制在很大程度上尚不清楚。在此，在普通人群（n=1103）中，发现 TSH 水平与颈动脉斑块患病率和内膜中层厚度均独立相关。一致地，在 小鼠中，TSH 受体缺失可减轻动脉粥样硬化形成，伴随着粥样斑块中血管炎症和巨噬细胞负担的减少。在骨髓特异性 - 缺陷 小鼠中也观察到了这些结果，这表明巨噬细胞是 TSH 的促炎和致动脉粥样硬化作用的关键靶标。体外实验进一步表明，TSH 在巨噬细胞中激活 MAPKs（ERK1/2、p38α 和 JNK）和 IκB/p65 通路，并增加炎症细胞因子的产生及其对单核细胞的募集。因此，本研究阐明了 TSH 作为动脉粥样硬化的独立危险因素，加重血管炎症并促进动脉粥样硬化形成的新机制。
