In vivo treatment of rat arterial adventitia with interleukin-1β induces intimal proliferation via the JAK2/STAT3 signaling pathway

Previous studies have indicated that adventitial inflammation is involved in the development of atherosclerosis. The aim of this study was to investigate the effect of arterial adventitia inflammation induced by interleukin (IL)-1β on intimal proliferation and the mechanisms involved in this process. The left common carotid artery adventitia of male rats in the experimental and control groups (25 rats/group) was wrapped with agar containing or without a sustained-release suspension of 2.5 µg IL-1β, respectively. Five animals in each group were randomly selected for sacrifice at 2 h, 8 h, 24 h, 48 h, and 1 week post-treatment. Hematoxylin and eosin staining was performed for to analyze the morphology of the adventitia. The expression of janus kinase (JAK)2, signal transducer and activator of transcription (STAT)3, phosphorylated (p-)JAK2 and p-STAT3 were detected by western blot analysis or immunohistochemistry staining. A model of adventitial inflammation was successfully created by wrapping IL-1β around the rat carotid artery. IL-1β treatment induced vascular smooth muscle cell proliferation and migration as well as intimal proliferation. In addition, the expression of p-JAK2 and p-STAT3 increased after IL-1β treatment. Furthermore, an inhibitor of JAK2/STAT3 pathway, AG490, suppressed IL-1β-induced intimal proliferation and phosphorylation of JAK2 and STAT3. Thus, the JAK2/STAT3 signaling pathway is involved in intimal proliferation caused by vascular adventitial inflammation. Inhibiting the JAK2/STAT3 signaling pathway may be a novel method for the clinical treatment of artery atherosclerosis.