Key regulator of vascular integrity
Since its discovery in 1993, the vasoactive peptide hormone Adrenomedullin (ADM) has attracted a great deal of interest as a multifunctional regulator of the vascular system, i.a. regulating angiogenesis and cardiovascular homeostasis . Adrenomedullin is mainly expressed and secreted by vascular endothelial cells and is best known for its vasodilatory activity . In addition, Adrenomedullin has been extensively described as key determinant of vascular integrity [4,5,6].
Molecular Mechanism of Action
Adrenonomedullin exerts its molecular action mainly via the stimulation of cAMP formation. ADM binds the G protein–coupled receptor CRLR (calcitonin receptor-like receptor) that is expressed both on vascular smooth muscle and vascular endothelial cells. CRLR is associated with one of three different accessory single-pass transmembrane proteins called RAMP1-3 . ADM only interacts with CRLR receptors that are accompanied by either RAMP2 or RAMP3 . Binding of Adrenomedullin to CRLR/RAMP2 or CRLR/RAMP3 on endothelial cells triggers downstream signaling pathways that affect endothelial barrier function and blood vessel permeability .