scholarly journals Critical Role of cAMP-response Element-binding Protein for Angiotensin II-induced Hypertrophy of Vascular Smooth Muscle Cells

2002 ◽  
Vol 277 (21) ◽  
pp. 18710-18717 ◽  
Author(s):  
Yuko Funakoshi ◽  
Toshihiro Ichiki ◽  
Kotaro Takeda ◽  
Tomotake Tokuno ◽  
Naoko Iino ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Angiotensin Ii ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Critical Role ◽  
Camp Response Element Binding ◽  
Camp Response Element ◽  
Element Binding Protein

scholarly journals cAMP attenuates angiotensin-II-induced Egr-1 expression via PKA-dependent signaling pathway in vascular smooth muscle cells

2017 ◽  
Vol 95 (8) ◽  
pp. 928-937 ◽  
Author(s):  
Estelle R. Simo-Cheyou ◽  
Viktoria Youreva ◽  
Ashok K. Srivastava
Keyword(s):  
Smooth Muscle ◽  
Angiotensin Ii ◽  
Vascular Smooth Muscle ◽  
Camp Response Element Binding ◽  
Ang Ii ◽  
Camp Response Element ◽  
Erk Phosphorylation ◽  
Vasp Phosphorylation ◽  
Element Binding Protein ◽  
Dose Dependent Fashion

cAMP has been shown to inhibit vascular smooth muscle cell proliferation and exerts a vasculoprotective effect. An upregulation of the early growth response protein-1 (Egr-1) expression has been linked with the development of atherosclerosis and intimal hyperplasia. We have recently demonstrated that angiotensin-II (Ang-II) stimulates Egr-1 expression via Ca2+/ERK-mediated cAMP-response element binding protein (CREB) activation. However, whether Ang-II-induced signaling leading to Egr-1 expression is modulated by cAMP remains unexplored. Therefore, in the present studies, we have examined the effect of cAMP on Ang-II-induced expression of Egr-1 and associated signaling pathways. Isoproterenol (ISO) and forskolin (FSK) attenuated Ang-II-induced Egr-1 expression in a dose-dependent fashion. In addition, dibutyryl-cAMP and benzoyl-cAMP, as well as isobutylmethylxanthine, attenuated Ang-II-induced Egr-1 expression. Moreover, inhibition of Ang-II-induced Egr-1 expression was accompanied by an increase in the phosphorylation of the vasodilator-activated phosphoprotein (VASP), and this was associated with a concomitant decrease in ERK phosphorylation. Blockade of PKA using H89 decreased VASP phosphorylation, restored Ang-II-induced ERK phosphorylation, and abolished ISO- and FSK-mediated inhibition of Ang-II-induced Egr-1 expression. In summary, these results suggest that PKA-mediated suppression of Ang-II-induced Egr-1 expression and phosphorylation of ERK may be among the mechanisms by which cAMP exerts its vasculoprotective effects.

Role of oxidative stress in angiotensin II-induced enhanced expression of Giα proteins and adenylyl cyclase signaling in A10 vascular smooth muscle cells

2007 ◽  
Vol 292 (4) ◽  
pp. H1922-H1930 ◽  
Author(s):  
Yuan Li ◽  
Georgios Lappas ◽  
Madhu B. Anand-Srivastava
Keyword(s):  
Oxidative Stress ◽  
Smooth Muscle ◽  
Angiotensin Ii ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Adenylyl Cyclase ◽  
Vascular Smooth Muscle Cells ◽  
Ang Ii ◽  
Enhanced Expression

We have previously reported that angiotensin II (ANG II) treatment of A10 vascular smooth muscle cells (VSMCs) increased inhibitory G proteins (Gi protein) expression and associated adenylyl cyclase signaling which was attributed to the enhanced MAP kinase activity. Since ANG II has been shown to increase oxidative stress, we investigated the role of oxidative stress in ANG II-induced enhanced expression of Giα proteins and examined the effects of antioxidants on ANG II-induced enhanced expression of Giα proteins and associated adenylyl cyclase signaling in A10 VSMCs. ANG II treatment of A10 VSMCs enhanced the production of O2− and the expression of Nox4 and P47phox, different subunits of NADPH oxidase, which were attenuated toward control levels by diphenyleneiodonium (DPI). In addition, ANG II augmented the expression of Giα-2 and Giα-3 proteins in a concentration- and time-dependent manner; the maximal increase in the expression of Giα was observed at 1 to 2 h and at 0.1–1.0 μM. The enhanced expression of Giα-2 and Giα-3 proteins was restored to control levels by antioxidants such as N-acetyl-l-cysteine, α-tocopherol, DPI, and apocynin. In addition, ANG II also enhanced the ERK1/2 phosphorylation that was restored to control levels by DPI. Furthermore, the inhibition of forskolin-stimulated adenylyl cyclase activity by low concentrations of 5′- O-(3-triotriphosphate) (receptor-independent Gi functions) and ANG II-, des(Glu18,Ser19,Glu20,Leu21,Gly22)atrial natriuretic peptide4-23-NH2 (natriuretic peptide receptor-C agonist), and oxotremorine-mediated inhibitions of adenylyl cyclase (receptor-dependent functions) that were augmented in ANG II-treated VSMCs was also restored to control levels by antioxidant treatments. In addition, Gsα-mediated diminished stimulation of adenylyl cyclase by stimulatory hormones in ANG II-treated cells was also restored to control levels by DPI. These results suggest that ANG II-induced enhanced levels of Giα proteins and associated functions in VSMCs may be attributed to the ANG II-induced enhanced oxidative stress, which exerts its effects through mitogen-activated protein kinase signaling pathway.

scholarly journals Role of Endogenous Angiotensin II in the Expression of Growth Factors and the Cell Cycle in Vascular Smooth Muscle Cells from SHR

1998 ◽  
Vol 39 (4) ◽  
pp. 561-561 ◽  
Author(s):  
Chikara Satoh ◽  
Noboru Fukuda ◽  
Atsushi Kubo ◽  
Hirobumi Kishioka ◽  
Mari Nakayama ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Smooth Muscle ◽  
Growth Factors ◽  
Angiotensin Ii ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells

scholarly journals Protein Arginine Methyltransferase 2 Inhibits Angiotensin II-Induced Proliferation and Inflammation in Vascular Smooth Muscle Cells

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Si-yu Zeng ◽  
Jing-fei Luo ◽  
Hai-yan Quan ◽  
Yun-bin Xiao ◽  
Yu-huan Liu ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Angiotensin Ii ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
Ang Ii ◽  
Arginine Methyltransferase ◽  
Vsmcs Proliferation

Objectives. Protein arginine methyltransferase 2 (PRMT2) protects against vascular injury-induced intimal hyperplasia; however, little is known about the role of PRMT2 in angiotensin II (Ang II)-induced VSMCs proliferation and inflammation. This research aims to determine whether PRMT2 inhibits Ang II-induced proliferation and inflammation of vascular smooth muscle cells (VSMCs). Materials and Methods. PRMT2 overexpression was used to elucidate the role of PRMT2 in Ang II-induced VSMCs proliferation and inflammation. Western blotting and reverse transcriptional PCR were adopted to detect protein and mRNA expression severally. Cell viability was evaluated by 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) assay and cell cycle distribution by flow cytometry. Results. Ang II significantly reduced mRNA and protein levels of PRMT2 in VSMCs in time-dependent and dose-dependent manner. Results of PRMT2 overexpression indicated that PRMT2 inhibited proliferation of VSMCs stimulated with 100 nmol/L Ang II for 24 hours. Furthermore, overexpression of PRMT2 reduced Ang II-induced production of proinflammatory cytokines such as interleukin 6 (IL-6) and interleukin 1β (IL-1β) in VSMCs. Conclusions. These findings suggest that PRMT2 alleviates Ang II-induced VSMCs proliferation and inflammation, providing a new mechanism about how Ang II mediated VSMCs proliferation and inflammation.

Abstract 667: Angiotensin II-induced Osteopontin Expression in Vascular Smooth Muscle Cells involves G q/11 , Ras, ERK, Src and Ets-1.

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Keiko Abe ◽  
Mari Ishida ◽  
Mariko Sawano ◽  
Hidekatsu Nakashima ◽  
Nwe Nwe Soe ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Angiotensin Ii ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Promoter Activity ◽  
Critical Role ◽  
Muscle Cells ◽  
Separate Experiment ◽  
Type I

Background : Osteopontin (OPN), an extracellular matrix component produced by vascular smooth muscle cells (VSMC) and monocytes in response to biological stressors, is a regulator of cellular proliferation and migration. Recent studies revealed that OPN also plays a critical role in the progression of atherosclerotic plaques and that angiotensin II (AngII) is a potent upregulator of OPN expression. Therefore, the goal of the present study was to characterize the signaling mechanisms whereby AngII increases OPN expression. Methods and Results : YM254890, a specific inhibitor of G q/11 , potently suppressed AngII-induced OPN expression and ERK1/2 activation. Among DN mutants of small G proteins (Ras, Rac, Rho), only DN-Ras completely suppressed AngII-induced OPN promoter activity. Dominant negative (DN)-MEK1 inhibited AngII-induced OPN promoter activity by 54%, while DN-c-Jun N-terminal kinase (JNK) or DN-p38MAP kinase had no effect. DN-Src and Csk suppressed AngII-induced OPN promoter activity by 49% and 71%, respectively. In addition, small interfering RNA against Ets-1 (a transcriptional factor downstream of ERK1/2) suppressed AngII-induced OPN expression by 54 ± 4.3%. In a separate experiment, rats were treated with the AngII type I receptor blocker, valsartan (1 mg/kg/day), or vehicle for 2 weeks after carotid artery balloon injury. The intima/media ratio and OPN expression were significantly lower in valsartan-treated rats than in vehicle-treated rats. Conclusion : These data suggest that AngII-induced OPN expression in VSMC is mediated by signaling cascades involving G q/11 , the Ras-ERK axis, and c-Src, and by the transcription factor, Ets-1. Further, OPN may play a role in AngII-induced neointimal formation. These signaling molecules may represent therapeutic targets for the prevention of pathological vascular remodeling in patients with hypertension and atherosclerosis.

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