Angiotensin II-induced growth of vascular smooth muscle cells is associated with modulation of cell surface area and platelet-derived growth factor receptor expression.
1. Excessive growth of vascular smooth muscle cells (VSMC) can lead to critical problems in the treatment of some vascular diseases. Recent studies suggest a connection between this abnormal growth of VSMC and the octapeptide hormone angiotensin (Ang) II. However, the growth-promotive potential of AngII on VSMC is unclear. 2. Using the novel AngII inhibitor E4177 and an original animal model, we confirmed that AngII does function in abnormal growth of VSMC induced after transplantation of vein grafts in an animal model. 3. Furthermore, using a primary culture of human aortic smooth muscle cells (HASMC), we found that AngII augmented the growth of HASMC in a serum-dependent manner and induced enlargement of the cell surface area in HASMC, both effects being nullified by E4177. The latter effect of AngII was associated with an increase in the expression level of platelet-derived growth factor (PDGF) receptors. In specimens obtained from the animal model, PDGF receptors were highly expressed. 4. These data obtained in vitro and in vivo imply that AngII has the potential to promote growth of VSMC and suggest that this growth promotion may be mediated by enlargement of the cell surface area.
Kuma
Sosei
S
Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. kuma@hiroshima-med.jrc.or.jp
Oki
Eiji
E
Onohara
Toshihiro
T
Komori
Kimihiro
K
Maehara
Yoshihiko
Y
D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D048429:Cell Size; D002478:Cells, Cultured; D004285:Dogs; D005434:Flow Cytometry; D006614:Hindlimb / Q000098:blood supply; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D007150:Immunohistochemistry; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects; D009389:Neovascularization, Pathologic / Q000473:pathology / Q000517:prevention & control; D011725:Pyridines / Q000494:pharmacology; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000037:antagonists & inhibitors; D017479:Receptors, Platelet-Derived Growth Factor / Q000096:biosynthesis*; D012039:Regional Blood Flow / Q000502:physiology
D020533:Angiogenesis Inhibitors; D047228:Angiotensin II Type 1 Receptor Blockers; D007093:Imidazoles; D011725:Pyridines; D000804:Angiotensin II; C083778:3-((2'-carboxybiphenyl-4-yl)methyl)-2-cyclopropyl-7-methyl-3H-imidazo(4,5-b)pyridine; D020797:Receptor, Platelet-Derived Growth Factor beta; D017479:Receptors, Platelet-Derived Growth Factor