Abstract：
OBJECTIVE:To explore the effect of urantide on atherosclerotic myocardial injury by antagonizing the urotensin II/urotensin II receptor (UII/UT) system and regulating the mitogen-activated protein kinase (MAPK) signalling pathway. METHODS:Atherosclerosis (AS) was established in rats by administering a high-fat diet and an intraperitoneal injection of vitamin D3. The effect of treatment with urantide (30 μg/kg), a UII receptor antagonist, for 3, 7, or 14 days on AS-induced myocardial damage was evaluated. RESULTS:The heart of rats with AS exhibited pathological changes suggestive of myocardial injury, and the serum levels of creatine kinase (CK) and lactate dehydrogenase (LDH) were significantly increased. Additionally, significant increases in the levels of UII, its receptor (G protein-coupled receptor 14, GPR14), p-P38, p-extracellular signal-regulated kinase (ERK) and p-c-Jun N-terminal kinase (JNK) were observed in the heart. Urantide improved pathological changes in the heart of rats with AS and reduced the serum CK and LDH levels. Additionally, the UII antagonist decreased the increased levels of UII, GPR14, p-P38, p-ERK and p-JNK in the heart. CONCLUSIONS:Urantide alleviates atherosclerotic myocardial injury by inhibiting the UII-GPR14 interaction and regulating the MAPK signalling pathway. We hypothesized that myocardial injury may be associated with the regulation of the MAPK signalling pathway.
journal_name
Life Scijournal_title
Life sciencesauthors
Zhao J,Miao G,Wang T,Li J,Xie Ldoi
10.1016/j.lfs.2020.118551subject
Has Abstractpub_date
2020-12-01 00:00:00pages
118551eissn
0024-3205issn
1879-0631pii
S0024-3205(20)31304-7journal_volume
262pub_type
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