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The murine type I CRS model was established and apela was subcutaneously infused for two weeks. Cardiac and renal functions were evaluated by echocardiography and blood biochemistry, respectively. The systemic and renal inflammatory responses were examined with molecular biological and histological methods. Human renal glomerular endothelial cells (RGECs) were used to evaluate the adhesion effect of monocytes in vitro. Compared to mice from the control group (CRS + vehicle), the plasma levels of N\u2010terminal pro\u2010brain natriuretic peptide, blood urea nitrogen and creatinine were significantly decreased, while the mean left ventricular ejection fraction was increased in apela\u2010treated CRS mice at the 4th week. The expression of monocyte chemoattractant protein\u20101 (MCP\u20101) and tumor necrosis factor\u2010\u03b1 (TNF\u2010\u03b1) in the circulation and kidney was decreased in apela\u2010treated mice compared with control mice, and apela improved cardio\u2010renal pathology in mice with type I CRS. Additionally, Apela significantly suppressed the expression of MCP\u20101, TNF\u2010\u03b1, intercellular adhesion molecule\u20101 and vascular intercellular adhesion molecule\u20101 in RGECs induced by angiotensin II (Ang II), and inhibited the promoting effect of Ang II on the adhesion of THP\u20101 cells to RGECs. Western blot results showed that the expression of phosphorylated nuclear factor kappa B (phospho\u2010NF\u03baB) in CRS mice was increased, but the expression of phospho\u2010NF\u03baB was down\u2010regulated after apela treatment. Furthermore, apela significantly inhibited the Ang II\u2010mediated increase in phospho\u2010NF\u03baB expression in RGECs in vitro, but the administration of an apelin peptide jejunum receptor (APJ) inhibitor blocked the inhibitory effect of apela. This study revealed that apela improves cardiorenal function and reduces systemic and renal inflammatory response in type I CRS mice and the apela\/APJ system may alleviate renal inflammatory responses by inhibiting the NF\u03baB signalling pathway.<\/jats:p>","DOI":"10.1096\/fj.202101030r","type":"journal-article","created":{"date-parts":[[2021,9,13]],"date-time":"2021-09-13T13:34:43Z","timestamp":1631540083000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Apela inhibits systemic and renal inflammatory reactions in mice with type I cardiorenal syndrome"],"prefix":"10.1096","volume":"35","author":[{"given":"Liangli","family":"Jin","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Medicine Affiliated Nanjing Brain Hospital Nanjing Medical University  Nanjing 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