Jiang Yun, Lu Linfang, Hu Youtao, Li Qiang, An Chaoqiang, Yu Xiaolan, Shu Le, Chen Ao, Niu Congcong, Zhou Lei, Yang Zaiqing
College of Life Science and Technology, Huazhong Agricultural University, Wuhan, China.
Clinical Laboratory, the Third Hospital of Wuhan, Wuhan, China.
Sci Rep. 2016 Feb 26;6:22193. doi: 10.1038/srep22193.
Resistin, an adipokine involved in insulin resistance (IR) and diabetes, has recently been reported to play a role in cardiovascular events. However, its effect on blood pressure (BP) and the underlying mechanisms remain unclear. In the present study, we showed that resistin induces hypertension and IR in wild type (WT) mice, but not in tlr4(-/-) mice. Resistin upregulated angiotensinogen (Agt) expression in WT mice, whereas it had no effect on tlr4(-/-) mice, or in mice treated with the angiotensin-converting enzyme inhibitor perindopril. Real-time PCR and chromatin immunoprecipitation further confirmed that resistin activates the renin-angiotensin system (RAS) via the TLR4/P65/Agt pathway. This finding suggested an essential role of resistin in linking IR and hypertension, which may offer a novel target in clinic on the study of the association between diabetes and hypertension.
抵抗素是一种参与胰岛素抵抗（IR）和糖尿病的脂肪因子，最近有报道称其在心血管事件中发挥作用。然而，其对血压（BP）的影响及潜在机制仍不清楚。在本研究中，我们发现抵抗素可诱导野生型（WT）小鼠发生高血压和IR，但对tlr4基因敲除（-/-）小鼠无此作用。抵抗素上调了WT小鼠血管紧张素原（Agt）的表达，而对tlr4（-/-）小鼠或用血管紧张素转换酶抑制剂培哚普利治疗的小鼠没有影响。实时PCR和染色质免疫沉淀进一步证实，抵抗素通过TLR4/P65/Agt途径激活肾素-血管紧张素系统（RAS）。这一发现表明抵抗素在连接IR和高血压方面起着重要作用，这可能为临床研究糖尿病与高血压之间的关联提供一个新的靶点。
