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