Adrenomedullin and endothelial barrier function

Bettina Temmesfeld-Wollbrück; Andreas C. Hocke; Norbert Suttorp; Stefan Hippenstiel

doi:10.1160/TH07-02-0128

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2007; 98(05): 944-951
DOI: 10.1160/TH07-02-0128

Theme Issue Article

Schattauer GmbH

Adrenomedullin and endothelial barrier function

Bettina Temmesfeld-Wollbrück

¹Department of Internal Medicine/Infectious Diseases and Pulmonary Medicine, Charité – Universitätsmedizin Berlin, Berlin, Germany

,

Andreas C. Hocke

¹Department of Internal Medicine/Infectious Diseases and Pulmonary Medicine, Charité – Universitätsmedizin Berlin, Berlin, Germany

,

Norbert Suttorp

¹Department of Internal Medicine/Infectious Diseases and Pulmonary Medicine, Charité – Universitätsmedizin Berlin, Berlin, Germany

,

Stefan Hippenstiel

¹Department of Internal Medicine/Infectious Diseases and Pulmonary Medicine, Charité – Universitätsmedizin Berlin, Berlin, Germany

› Author Affiliations

Abstract

Summary

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.

Keywords

Adrenomedullin - endothelium - permeability - inflammation - sepsis

Full Text

References

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