Adrenomedullin antagonizes angiotensin II-stimulated proliferation of human aortic smooth muscle cells.
The vasodilating peptide adrenomedullin has been reported to regulate vascular tone as well as proliferation and differentiation of various cell types in an autocrine/paracrine manner. Conflicting data have been reported on the adrenomedullin (AM) effect on vascular smooth muscle cell proliferation, a process involved in the progression of vascular remodeling and atherosclerotic lesion. In this paper we investigate the effect of AM on proliferation of human aorta smooth muscle cell (HASMC). AM showed a potent dose-dependent inhibiting effect on angiotensin II (AngII) induced-proliferation and a stimulatory effect on proliferation of quiescent cells. The cAMP/PKA pathway was involved in the AM inhibitory effect of AngII-induced proliferation in HASMC. PI3K/Akt and ERK pathways were involved in the proliferative effect exerted by AM per se. Our results suggest that AM plays a role in the regulation of HASMC growth antagonizing the AngII effect and may be involved in conditions of altered regulation of the blood vessels.
Rossi
Fabio
F
Dipartimento di Fisiopatologia Medica, V Clinica Medica, Università La Sapienza, Facoltà di Medicina, Policlinico Umberto I, Viale del Policlinico, 00161 Rome, Italy.
Bertone
Cora
C
Petricca
Silvia
S
Santiemma
Vittorio
V
D053607:Adrenomedullin / Q000494:pharmacology / Q000502:physiology*; D000804:Angiotensin II / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D001011:Aorta / Q000166:cytology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D006801:Humans; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
D000804:Angiotensin II; D053607:Adrenomedullin; C494918:AKT1 protein, human; D051057:Proto-Oncogene Proteins c-akt; D048052:Mitogen-Activated Protein Kinase 3