Adrenomedullin and cardiovascular responses in sepsis TU Jie March 19,2004
Adrenomedullin and cardiovascular responses in sepsis TU Jie March 19, 2004
Introduction 。 Sepsis,septic shock:the major cause of high mortality in intensive care units Adrenomedullin (ADM or AM):produced in abnormally large quantities
Introduction • Sepsis, septic shock: the major cause of high mortality in intensive care units • Adrenomedullin (ADM or AM): produced in abnormally large quantities
185 PreproAM Signal Peptide ProAM PAMP (20 a.a.) AM(52a.a.) NH29®OS@QN 国o009®00o0 @09009900®90 00008080D国9 ®③®①③0O@9 -CONH2
• Molecular structure of AM: 52-amino acid peptide, first reported in 1993 • Distribution of AM: plasma, heart, lung, kidney, stomach, endothelial cells, smooth muscles, epithelial cells …
Molecular structure of AM:52-amino acid peptide,first reported in 1993 Distribution of AM:plasma,heart,lung, kidney,stomach,endothelial cells,smooth muscles,epithelial cells
• Molecular structure of AM: 52-amino acid peptide, first reported in 1993 • Distribution of AM: plasma, heart, lung, kidney, stomach, endothelial cells, smooth muscles, epithelial cells …
Functions of AM:endocrine factor as well as a local autocrine and paracrine factor with cardiovascular and renal actions be of particular interest in pathophysiology of sepsis
• Functions of AM: endocrine factor as well as a local autocrine and paracrine factor with cardiovascular and renal actions be of particular interest in pathophysiology of sepsis
AM receptor and AM-binding protein the existence of AM binding sites in blood vessels,heart,lung,spleen,liver .. two AM receptor subtypes:CGRP-like receptor and AM specific receptor
AM receptor and AM-binding protein • the existence of AM binding sites in blood vessels, heart, lung, spleen, liver … • two AM receptor subtypes: CGRP-like receptor and AM specific receptor
RAMPs:a novel family of single transmembrane proteins,three isoforms CRLR:calcitonin-receptor-like receptor,an orphan recptor with seven transmembrane domains RAMP1/CRLR=CGRP recpto ·the function of RAMP/CRLR complex RAMP2/CRLR=AM receptor (depending on the expression of RAMP)】 RAMP3/CRLR AM receptor
• RAMPs: a novel family of single transmembrane proteins, three isoforms • CRLR: calcitonin-receptor-like receptor, an orphan recptor with seven transmembrane domains • the function of RAMP/CRLR complex (depending on the expression of RAMP) RAMP1/CRLR=CGRP recptor RAMP2/CRLR=AM receptor RAMP3/CRLR ? AM receptor
AM binding protein:120 and/or 140 kDa in mammalian blood AMBP-1:identical to human complement factor H AMBP-1 may affect the function and bioactivity of AM The circulating level of AMBP-1 during sepsis: remains unknown
• AM binding protein: 120 and/or 140 kDa in mammalian blood • AMBP-1: identical to human complement factor H • AMBP-1 may affect the function and bioactivity of AM • The circulating level of AMBP-1 during sepsis: remains unknown
Upregulation of AM in sepsis 1000 ● 751 日： 100 8 3.0 士 15 10- 0.0 Hours after CLP or Sham-operation Control Septic Shock Plasma concentration of adrenomedullin in Changes in cardiac ADM levels at 5 and 20 h after patients with septic shockand in control cecal ligation and puncture(CLP)or sham-operation patients."p <0.01 between groups. (sham).*P<0.05 versus the respective sham. Nishio K.Akai Y.Murao Y et al.Increased plasma Zhou M.Chaudry IH.Wang P.Adrenomedullin is upregulated in the tions of adrenome ation 1 of ascular tone in patients with septic shock:Cnit Care Med. and aorta durin nd late stages of sepsis.Biochim Biop Acia.1999.2414532273-83
Upregulation of AM in sepsis Plasma concentration of adrenomedullin in patients with septic shock and in control patients. **p <0.01 between groups. Changes in cardiac ADM levels at 5 and 20 h after cecal ligation and puncture (CLP) or sham-operation (sham). *P<0.05 versus the respective sham. Nishio K, Akai Y, Murao Y et al. Increased plasma concentrations of adrenomedullin correlate with relaxation of vascular tone in patients with septic shock: Crit Care Med. 1997, 25(6):953-7 Zhou M, Chaudry IH, Wang P. Adrenomedullin is upregulated in the heart and aorta during the early and late stages of sepsis. Biochim Biophys Acta. 1999 , 24;1453(2):273-83
3001 ·LPS:stimulating AM production 200 100 Control LPS Jean Marc Hyvelin,Qixian Shan,Jean Pierre Bourreau. Adrenomedullin:a cardiac depressant factor in septic shock.J Card Surg,2002,17(4):328-35
• LPS: stimulating AM production Control LPS 0 100 200 300 ** serum AM (fmol/ml) Jean Marc Hyvelin, Qixian Shan, Jean Pierre Bourreau. Adrenomedullin: a cardiac depressant factor in septic shock. J Card Surg, 2002, 17(4):328-35