Adrenomedullin in sinusoidal endothelial cells play protective roles against cold injury of liver

Peptides
Nobuyoshi IinumaTakayuki Shindo

Abstract

Donor organ damage caused by cold preservation is a major problem affecting liver transplantation. Cold preservation most easily damages liver sinusoidal endothelial cells (LSECs), and information about the molecules modulating LSECs function can provide the basis for new therapeutic strategies. Adrenomedullin (AM) is a peptide known to possess anti-apoptotic and anti-inflammatory properties. AM is abundant in vascular endothelial cells, but levels are comparatively low in liver, and little is known about its function there. In this study, we demonstrated both AM and its receptors are expressed in LSECs. AM treatment reduced LSECs loss and apoptosis under cold treatment. AM also downregulated cold-induced expression of TNFalpha, IL1beta, IL6, ICAM1 and VCAM1. AM reduced apoptosis and expression of ICAM1 and VCAM1 in an in vivo liver model subjected to cold storage. Conversely, apoptosis was exacerbated in livers from AM and RAMP2 (AM receptor activity-modifying protein) knockout mice. These results suggest that AM expressed in LSECs exerts a protective effect against cold-organ damage through modulation of apoptosis and inflammation.

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Citations

Oct 8, 2013·The International Journal of Biochemistry & Cell Biology·Elisabetta Liverani, Carolyn Paul
Sep 6, 2011·Allergologia et immunopathologia·E KucukosmanogluA Balat
Nov 11, 2011·Amyloid : the International Journal of Experimental and Clinical Investigation : the Official Journal of the International Society of Amyloidosis·Giovanni PalladiniGiampaolo Merlini
Jun 8, 2017·Experimental and Therapeutic Medicine·Lian-Cheng ZhangWei Liu

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