title: Recombinant Human Annexin A5 Can Repair the Disrupted Cardiomyocyte Adherens Junctions in Endotoxemia.
abstract: Recombinant human annexin A5 (Anx5) is known to protect cardiac function during endotoxemia, although the underlying mechanisms have yet to be elucidated. In this study, we demonstrated that Anx5 could repair the disrupted cardiomyocyte adherens junctions and improve the myocardial contractile function in lipopolysaccharide (LPS)-induced endotoxemia. Mechanistic studies revealed that Anx5 could antagonize the disassociation between p120-catenin (p120) and N-cadherin as well as the dephosphorylation of p120 in LPS-treated cardiomyocytes. Small interference RNA and specific inhibitors experiment demonstrated that Anx5 regulated p120 functions by inhibition of p21-activated kinase 5 in a protein kinase Cα-dependent way. Moreover, Anx5 could inhibit nuclear factor κB activation and downregulate the level of inflammatory cytokines, such as tumor necrosis factor α and interleukin 1β, which contributed to improving tissue pathological damage in LPS-induced mouse endotoxemia model. Taken together, Anx5 could protect cardiomyocytes adherens junctions and improve myocardial contractile function via regulation of p120 and anti-inflammation in LPS-induced endotoxemia. This study provided novel insights in the prevention and treatment of septic shock.
authors: *Department of Anesthesiology, Qianfoshan Hospital of Shandong University, Jinan, Shandong, People's Republic of China; and †Department of Surgical Neurology, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
authors: Changping
authors: C
authors: Gu
authors: Mengjie
authors: M
authors: Liu
authors: Tao
authors: T
authors: Zhao
authors: Lijie
authors: L
authors: Zhai
authors: Yuelan
authors: Y
authors: Wang
mesh_terms: D022005:Adherens Junctions / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D017304:Annexin A5 / Q000494:pharmacology*; D051177:Catenins / Q000378:metabolism; D004195:Disease Models, Animal; D019446:Endotoxemia / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D053583:Interleukin-1beta / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D051379:Mice; D009200:Myocardial Contraction / Q000187:drug effects; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D017304:Annexin A5; D051177:Catenins; C587672:IL1B protein, mouse; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha