Endothelial Stimulation of Sodium Pump in Cultured Vascular Smooth Muscle

Hypertension ◽  
1995 ◽  
Vol 26 (1) ◽  
pp. 177-185 ◽  
Author(s):  
Juliana Redondo ◽  
Concepción Peiró ◽  
Leocadio Rodríguez-Mañas ◽  
Mercedes Salaices ◽  
Jesús Marín ◽  
...  
1991 ◽  
Vol 69 (1) ◽  
pp. 39-44 ◽  
Author(s):  
J C Allen ◽  
R M Medford ◽  
X Zhao ◽  
T A Pressley

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Marius Vantler ◽  
Lenard Mustafov ◽  
Evren Caglayan ◽  
Stephan Rosenkranz

Proliferation, migration, and apoptosis of vascular smooth muscle cells (VSMC) are pivotal determinants of the pathogenesis of vascular diseases, which are mainly controlled by growth factor dependent activation of PI 3-Kinase (PI3K). Growth factors like platelet-derived growth factor (PDGF) activate class IA PI3Ks containing one of three p110 catalytic subunits (p110alpha, p110beta, and p110delta). We investigated the specific function of these isoforms for PDGF-controlled proliferation, migration, and apoptosis of VSMC using novel isoform-specific inhibitors. PDGF-dependent proliferation and migration solely depended on p110alpha. Stimulation of VSMC with PDGF-BB (50 ng/ml) mediated a 2.5±0.4 increase ( p <0.05) of DNA-synthesis (BrdU incorporation assay) and induced a 3.4+/−0.7 fold increase ( p <0.05) of VSMC migration (modified Boyden-chamber). Inhibition of p110alpha with PIK075 (1 μ M, Ki=100 nM) completely abrogated PDGF-dependent DNA-synthesis and migration ( p <0,05), whereas inhibitors against p110beta (TGX 221, 1 μ M) or p110delta (IC87114 1 μ M) had no influence. Consistently, PDGF-induced DNA-synthesis and migration were suppressed by siRNA-dependent downregulation of p110alpha ( p <0,05) whereas p110beta or p110delta knockdown had no effect. Interestingly, stimulation of VSMC with PDGF-BB (50 ng/ml) induced anti- or proapoptotic effects depending on the duration of PDGFR activation. Incubation of VSMC with H 2 O 2 (50 μ M, 16h) led to a 2.8±0.7 fold increase ( p >0.05) of apoptosis (Cell Death Detection ELISA). Simultanous addition of PDGF-BB (50 ng/ml) significantly diminished the H 2 O 2 -induced apoptosis (52±7%, p >0.05). In contrast, prestimulation with PDGF-BB 24h prior to the addition of H 2 O 2 led to an increase of H 2 O 2 -induced apoptosis (7.8±1.3, p >0.05). The anti- as well as the proapoptotic effect depended strictly on p110alpha as PIK075 (1 μ M, p <0,05) or p110alpha specific siRNA completely abrogated PDGF-BB-mediated pro- as well as antiapoptotic effects. Our results demonstrate that only the catalytical PI3K subunit p110alpha mediates the growth factor-induced atherogenic responses. Therefore, p110alpha represents an interesting therapeutic target for prevention of atherosclerosis and restenosis formation.


Hypertension ◽  
2000 ◽  
Vol 36 (suppl_1) ◽  
pp. 709-709
Author(s):  
Mizuo Mifune ◽  
Hiroyuki Sasamura ◽  
Hideaki Nakaya ◽  
Ryoko Shimizu-Hirota ◽  
Matsuhiko Hayashi ◽  
...  

P84 Previously, we and others have shown that angiotensin II enhances vascular smooth muscle cell extracellular matrix synthesis via stimulation of the type 1 angiotensin (AT1) receptor. Recently, expression of the type 2 (AT2) receptor has been confirmed in the adult vasculature, but its role in vascular remodeling has not yet been fully defined. In particular, conflicting data from in vivo studies have reported that AT2 receptor inhibition may either attenuate or enhance vascular hypertrophy and fibrosis. The aim of this study was to clarify the effects of direct stimulation of AT2 receptors on collagen synthesis in vascular smooth muscle cells in vitro. Firstly, retroviral gene transfer was used to supplement adult vascular smooth muscle cells with AT2 receptors to mimic the vasculature in vivo. Treatment of these cells with the AT2 receptor agonist CGP42212A (10-7 mol/L) alone did not cause a significant change in p42/p44 MAP kinase activity, but caused a modest (33%) decrease in protein tyrosine phosphatase activity. Treatment with CGP42112A also caused a dose- and time-dependent increase in both cell-associated and secretory collagen synthesis (148+17% of control at 48 h, p<0.05) which was completely inhibited by the AT2 receptor antagonist PD123319, but unaffected by the AT1 receptor antagonist losartan. The AT2 receptor-mediated stimulation of collagen synthesis was unaffected by tyrosine phosphatase inhibitors sodium orthovanadate and okadaic acid, but attenuated by pretreatment with pertussis toxin or Galphai antisense oligonuclotides. These results suggest that direct AT2 receptor stimulation can increase rather than decrease collagen synthesis in vascular smooth muscle cells, and suggest a role for Galphai in the AT2 receptor-mediated effects.


2019 ◽  
Vol 471 (6) ◽  
pp. 889-899 ◽  
Author(s):  
Nadeshda Schelski ◽  
Trang T. D. Luong ◽  
Florian Lang ◽  
Burkert Pieske ◽  
Jakob Voelkl ◽  
...  

1992 ◽  
Vol 92 (1) ◽  
pp. 1-7 ◽  
Author(s):  
Masanobu Koide ◽  
Yasuhiro Kawahara ◽  
Terutaka Tsuda ◽  
Yoshihiro Ishida ◽  
Kozui Shii ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document