Urantide alleviates the symptoms of atherosclerotic rats in vivo and in vitro models through the JAK2/STAT3 signaling pathway.

Atherosclerosis is the leading cause of human death, and its occurrence and development are related to the urotensin II (UII) and UII receptor (UT) system and the biological function of vascular smooth muscle cells (VSMCs). During atherosclerosis, impaired biological function VSMCs may promote atherosclerotic plaque formation. The Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) pathway is an important mediator of signal transduction; however, the role of this signaling pathway in atherosclerosis and VSMCs remains unknown. This study aimed to investigate the effects of urantide on the JAK2/STAT3 signaling pathway in atherosclerosis. We examined the effect of urantide on the UII/UT system and the JAK2/STAT3 signaling pathway in a high fat diet induced atherosclerosis rat model and studied the effect and mechanism of urantide on the phenotypic transformation of VSMCs. We found that the UII/UT system and JAK2/STAT3 signaling pathway were highly activated in the thoracic aorta in atherosclerotic rats and in ox-LDL- and UII-induced VSMCs. After urantide treatment, the pathological changes in atherosclerotic rats were effectively improved, and the activities of the UII/UT system and JAK2/STAT3 signaling pathway were inhibited. Moreover, urantide effectively inhibited proliferation and migration and reversed the phenotypic transformation of VSMCs. These results demonstrated that urantide may control the JAK2/STAT3 signaling pathway by antagonizing the UII/UT system, thereby maintaining the biological function of VSMCs and potentially preventing and curing atherosclerosis.