title: Adrenomedullin and endothelial barrier function.
abstract: Although loss of endothelial barrier function is a hallmark of every acute inflammation and contributes to fatal loss of organ function during severe infections, there is no sufficient therapy for stabilization of endothelial barrier function. Endogenous peptide adrenomedullin (AM) serum levels were shown to be increased during severe infection including sepsis and septic shock. In different in-vitro and in-vivo models AM acted as a potent therapeutic endothelial barrier function-stabilizing agent. Activation of specific receptors by AM results in elevation of second messenger cAMP. AM inhibits actin-myosin based endothelial cell contraction and junctional disassembly, thereby preventing paracellular permeability and oedema formation. The peptide furthermore possesses several protective cardiovascular qualities, including protection of the microcirculation during inflammation, and was proven as an efficient counter-regulatory molecule in various models of sepsis and septic shock. Overall, AM may be an attractive molecule to combat against cardiovascular malfunction during severe infection.
authors.affiliation: Department of Internal Medicine/Infectious Diseases and Pulmonary Medicine, Charité--Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany.
authors.forename: Bettina
authors.initials: B
authors.lastname: Temmesfeld-Wollbrück
authors.forename: Andreas C
authors.initials: AC
authors.lastname: Hocke
authors.forename: Norbert
authors.initials: N
authors.lastname: Suttorp
authors.forename: Stefan
authors.initials: S
authors.lastname: Hippenstiel
mesh_terms: D053607:Adrenomedullin / Q000097:blood* / Q000627:therapeutic use; D002316:Cardiotonic Agents; D004730:Endothelium, Vascular / Q000502:physiology*; D006801:Humans; D007249:Inflammation; D010539:Permeability; D018805:Sepsis
chemical_list: C507862:ADM protein, human; D002316:Cardiotonic Agents; D053607:Adrenomedullin