Somatostatin: a hormone for the heart?
Somatostatin (somatotropin release inhibitory factor; SRIF) peptides are widely distributed throughout the mammalian body and act through a family of genetically distinct, guanine nucleotide regulatory protein coupled (G-protein-coupled), cell surface receptors (sst(1-5)). Compelling evidence shows that SRIF and SRIF peptidyl analogs modulate vascular function, with actions upon smooth muscle and endothelium. SRIF receptors are known to exist in the carotid endothelium, a principal target for the pro-inflammatory cascade that accompanies coronary artery disease. SRIF-14 and SRIF analogs are anti-inflammatory but the molecular mechanism involved remains unclear. Since crucial steps in the endothelial inflammation response include endothelial activation by cytokines, adhesion molecule expression and cell-monocyte interactions, peptide agents that inhibit these steps might provide a novel strategy for reducing vascular inflammation. SRIF, acting through its cognate receptors, modulates a variety of intracellular effectors that are linked to inflammation including phosphotyrosine phosphatases, the extracellular regulated protein kinase 1 and 2 (ERK1/2) cascade, adenylyl cyclase and endothelial nitric oxide synthase. Directly or indirectly, SRIF also functions to inhibit endothelial cell proliferation and induce apoptosis. A detailed understanding of SRIF actions could provide a rational basis for using SRIF ligands in controlling vascular inflammation and inhibiting cytokine signaling, critical events in atherogenesis.
Badway
Amy C
AC
Dept. of Biology, Seton Hall University, South Orange, NJ 07079, USA.
Blake
Allan D
AD
D000818:Animals; D006727:Hormone Antagonists / Q000494:pharmacology*; D006801:Humans; D017481:Receptors, Somatostatin / Q000187:drug effects; D013004:Somatostatin / Q000502:physiology*
D006727:Hormone Antagonists; D017481:Receptors, Somatostatin; D013004:Somatostatin