脂肪因子 Chemerin 可刺激载脂蛋白 E 小鼠的动脉粥样硬化进展。
Adipokine Chemerin Stimulates Progression of Atherosclerosis in ApoE Mice.
机构信息
Department of Cardiology, Shenzhen People's Hospital, The Second Affiliated Hospital of Jinan Medical College, Shenzhen 518020, China.
Department of Gerontology, Shenzhen People's Hospital, The Second Affiliated Hospital of Jinan Medical College, Shenzhen 518020, China.
出版信息
Biomed Res Int. 2019 Oct 31;2019:7157865. doi: 10.1155/2019/7157865. eCollection 2019.
BACKGROUND
Vascular remodeling is the most critical pathogenesis of atherosclerosis. Adipokine chemerin was known for its relationship with obesity as well as metabolism. Most recently, chemerin was found to play a crucial role in the pathologic process of cardiovascular diseases including coronary heart disease. In this study, we surveyed the role of chemerin in progression of atherosclerosis in ApoE mice.
OBJECTIVE
To investigate the relationship between chemerin and progression of atherosclerosis in ApoE mice and its mechanism.
METHODS
8-week-old ApoE mice were fed with high-fat diet to induce the atherosclerosis model. Adenoviruses were transfected for knockdown or overexpression of chemerin gene into aorta. Serums and aortic tissues of ApoE mice were obtained after feeding high-fat diet for 16 weeks. HE staining and oil red staining were performed to evaluate aortic plaque. ELISA was performed to explore serum levels of tumor necrosis factor- (TNF-), interleukin-1 (IL-1), and transforming growth factor-1 (TGF-1). Real-time PCR and western blotting were carried out to investigate the mRNA and protein levels of chemerin, nuclear factor-B p65 (NF-Bp65), proliferating cell nuclear antigen (PCNA), phosphorylated p38 mitogen-activated protein kinase (-p38-MAPK), phosphorylated c-Jun N-terminal kinase (-JNK), and phosphorylated extracellular signal regulated kinase 1/2 (-ERK 1/2).
RESULT
Aortic plaque formation was significantly induced by high-fat diet in ApoE mice. Simultaneously, elevated serum levels of TNF- and IL-1 and elevated mRNA and protein levels of chemerin, NF-Bp65, PCNA, -p38-MAPK, -JNK, and -ERK 1/2 were found in ApoE mice. After aortic chemerin gene was inhibited by adenovirus, aortic atherosclerosis induced by high-fat diet was significantly meliorated, serum levels of TNF- and IL-1 decreased, mRNA and protein levels of NF-Bp65, PCNA, -p38-MAPK, -JNK, and -ERK 1/2 decreased simultaneously.
CONCLUSION
Our study revealed that chemerin stimulated the progression of atherosclerosis in ApoE mice.
背景
血管重构是动脉粥样硬化最关键的发病机制。脂肪因子趋化素（chemerin）因其与肥胖和代谢的关系而被人所知。最近，发现趋化素在包括冠心病在内的心血管疾病的病理过程中起着至关重要的作用。在本研究中，我们调查了趋化素在 ApoE 小鼠动脉粥样硬化进展中的作用及其机制。
目的
探讨趋化素与 ApoE 小鼠动脉粥样硬化进展的关系及其机制。
方法
将 8 周龄 ApoE 小鼠用高脂饮食喂养以诱导动脉粥样硬化模型。用腺病毒转染将趋化素基因敲低或过表达到主动脉。用高脂饮食喂养 16 周后，获取 ApoE 小鼠的血清和主动脉组织。行 HE 染色和油红染色评估主动脉斑块。酶联免疫吸附试验（ELISA）检测肿瘤坏死因子-（TNF-）、白细胞介素-1（IL-1）和转化生长因子-1（TGF-1）的血清水平。实时 PCR 和 Western blot 检测趋化素、核因子-B p65（NF-Bp65）、增殖细胞核抗原（PCNA）、磷酸化 p38 丝裂原活化蛋白激酶（-p38-MAPK）、磷酸化 c-Jun N 端激酶（-JNK）和磷酸化细胞外信号调节激酶 1/2（-ERK 1/2）的 mRNA 和蛋白水平。
结果
高脂饮食显著诱导 ApoE 小鼠主动脉斑块形成。同时，ApoE 小鼠血清中 TNF-和 IL-1 水平升高，趋化素、NF-Bp65、PCNA、-p38-MAPK、-JNK 和 -ERK 1/2 的 mRNA 和蛋白水平升高。用腺病毒抑制主动脉趋化素基因后，高脂饮食诱导的主动脉粥样硬化明显改善，血清中 TNF-和 IL-1 水平降低，NF-Bp65、PCNA、-p38-MAPK、-JNK 和 -ERK 1/2 的 mRNA 和蛋白水平同时降低。
结论
本研究揭示了趋化素促进 ApoE 小鼠动脉粥样硬化的进展。
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