Ghrelin inhibits angiotensin II-induced migration of human aortic endothelial cells.
Ghrelin, the endogenous ligand for the GH secretagogue receptor, is produced by the oxyntic cells of the stomach and is involved in the regulation of energy balance. However, an increasing number of direct ghrelin cardiovascular effects, and, among them, high ghrelin binding in atherosclerotic coronary arteries, are being reported. We investigated whether ghrelin affects migration of human aorta endothelial cells (HAEC). HAEC bound ghrelin in specific, saturable manner. Ghrelin, as such, did not affect HAEC migration, however it inhibited the angiotensin II-induced migration, and this effect was inhibited by the antagonist (D-Lys(3))-GHRP-6. In HAEC, ghrelin elicited increased intracellular concentration of cAMP that was involved in its effect on AngII-induced HAEC migration, as the AMP cyclase inhibitor SQ22.536 and PKA inhibitor KT5720, respectively, inhibited and blunted it. These findings suggest a role of ghrelin in the control of endothelial cell migration and its possible involvement in vascular changes present in disorders characterized by low plasma ghrelin.
Rossi
Fabio
F
Dipartimento di Fisiopatologia Medica, V Clinica Medica Policlinico Umberto I Università La Sapienza di Roma, Rome, Italy.
Bertone
Cora
C
Petricca
Silvia
S
Santiemma
Vittorio
V
D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000067956:Adenylyl Cyclase Inhibitors; D000804:Angiotensin II / Q000037:antagonists & inhibitors*; D001011:Aorta / Q000166:cytology; D002227:Carbazoles / Q000494:pharmacology; D002465:Cell Movement / Q000187:drug effects*; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D054439:Ghrelin; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology; D036361:Peptide Hormones / Q000378:metabolism / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011758:Pyrroles / Q000494:pharmacology
D000067956:Adenylyl Cyclase Inhibitors; D002227:Carbazoles; C520836:GHRP-6, Lys(3)-; D054439:Ghrelin; D007211:Indoles; D009842:Oligopeptides; D036361:Peptide Hormones; D011758:Pyrroles; D000804:Angiotensin II; C017759:9-(tetrahydro-2-furyl)-adenine; C057416:KT 5720; D000242:Cyclic AMP; D051057:Proto-Oncogene Proteins c-akt; D017868:Cyclic AMP-Dependent Protein Kinases; D000225:Adenine