Characterization of the angiotensin II AT<sub>1</sub> receptor subtype involved in DNA synthesis in cultured vascular smooth muscle cells

Briand, Véronique; Riva, Laurence; Galzin, Anne-Marie

doi:10.1111/j.1476-5381.1994.tb13210.x

Cited by 14 publications

(6 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…34 In the experiments using cultured rat or human mesangial cells, losartan inhibited the angiotensin II-stimulated hypertrophy [35][36][37] and proliferation 36,37 of the mesangial cells. Similar results have been reported in the experiments using cultured vascular smooth muscle cells; namely, angiotensin II with or without PDGF or EGF stimulated the proliferation of cultured smooth muscle cells, which was inhibited by losartan [38][39][40] or candesartan. 41 Based on the results shown in this paper and the findings reported in the literature, it is summarised that angiotensin AT 1 receptor antagonists protect against end-organ damage which is produced in the models of rats.…”

Section: Discussionsupporting

confidence: 88%

Angiotensin AT1 receptor antagonism and protection against cardiovascular end-organ damage

Nishikawa

1998

J Hum Hypertens

View full text Add to dashboard Cite

This review describes how angiotensin AT 1 receptor antagonists (eg, candesartan cilexetil, losartan) effectively protect against end-organ damage including stroke, cardiac hypertrophy, renal dysfunction, glomerulosclerosis, and/or vascular hypertrophy in the models of stroke-prone spontaneously hypertensive rats (SHRSP), SHR, DOCA/salt hypertensive rats, Dahl hypertensive rats and/or 5/6 nephrectomised rats. Particularly in SHRSP and DOCA/salt hypertensive rats, candesartan cilexetil markedly reduced the incidence of stroke and renal injury even at doses which had no effect on blood pressure (BP), suggesting that the tissue protective effects of angiotensin AT 1 antagonists are not attributable simply to the normalisation of BP. In the heart, kidney and vascular tissues of SHRSP and the kidney of DOCA/salt hypertensive rats, the mRNA

show abstract

Section: Discussionsupporting

confidence: 88%

Angiotensin AT1 receptor antagonism and protection against cardiovascular end-organ damage

Nishikawa

1998

J Hum Hypertens

View full text Add to dashboard Cite

show abstract

“…In this regard, ANG2-induced hypertrophy of cardiac myocytes is mediated by AT1 receptors [17, 37]; however, this hypertrophic response is tempered by the concomitant activation of AT2 receptors which have antigrowth effects [37]. Similarly, ANG2 induces proliferation of vascular smooth muscle via AT1-dependent mechanisms [38]; whereas, AT2 receptor activation has antiproliferative effects [39, 40]. Indeed, growing literature suggests that the pathologic effects of AT1 receptor activation may be counterbalanced by the opposing actions of AT2 receptors in many cell types [4].…”

Section: Discussionmentioning

confidence: 99%

Transactivation of the Epidermal Growth Factor Receptor by Angiotensin II in Glomerular Podocytes

Flannery

Spurney²

2006

Nephron Exp Nephrol

View full text Add to dashboard Cite

Background/Aims: Activation of angiotensin II (ANG2) receptors stimulates extracellular signal-regulated kinases (ERKs) that, in some cell systems, are mediated by transactivating the epidermal growth factor (EGF) receptor (EGFR) through mechanisms involving matrix metalloprotease (MMP)-stimulated processing of heparin-binding EGF (HB-EGF) from its precursor. Methods: The signaling pathways linked to ANG2-dependent ERK activation were determined in an immortalized mouse podocyte cell line by monitoring ANG2-stimulated phosphorylation of ERK1/2. Results: ANG2 induced transient ERK phosphorylation that was maximal at 5 min and then rapidly dissipated. ANG2-dependent ERK activation was inhibited by: (1) the type-1 ANG2-selective antagonist losartan; (2) the type-2 ANG2-selective antagonist PD123319; (3) an inhibitor of MMP2/9; (4) the EGFR kinase inhibitor AG1478, and (5) the HB-EGF antagonists CRM197 and heparin. ANG2-dependent ERK activation was mediated by both protein kinase C (PKC)- and calcium-dependent mechanisms and was associated with tyrosine phosphorylation of EGFR. To determine if ANG2-dependent HB-EGF release could act in a paracrine fashion on adjacent cells, HEK293 cells were stably transfected with green fluorescent protein-tagged ERK2 (GFP-ERK2). In stably transfected HEK293 cells, EGF stimulated phosphorylation of endogenous ERK1/2 as well as GFP-ERK2. In contrast, ANG2 had no effect on ERK phosphorylation in stably transfected HEK293 cells. When podocytes were co-cultured with stably transfected HEK293 cells, however, treatment with ANG2 rapidly stimulated GFP-ERK2 phosphorylation. Both the MMP2/9 inhibitor and AG1478 attenuated ANG2-dependent phosphorylation of GFP-ERK2 in the co-culture system. Conclusions: These data indicate that ERK activation is induced by ANG2 in podocytes by mechanisms involving ANG2-dependent release of HB-EGF which, in turn, may act in an autocrine and paracrine fashion to stimulate ERK activity.

show abstract

“…Angiotensin II and the angiotensin system have been shown to be intimately involved in the vessel’s response to injury and its remodeling (19). Angiotensin II is a G protein agonist that activates a Gαq-coupled receptor (20) and stimulates smooth muscle cell proliferation (21, 22). Angiotensin II signaling is associated with increases in MMP-9 levels and an increase in PAI-1 expression or activity (23, 24).…”

Section: Discussionmentioning

confidence: 99%

Gαq G proteins modulate MMP-9 gelatinase during remodeling of the murine femoral artery

Zou

2013

Journal of Surgical Research

View full text Add to dashboard Cite

Background Vessels heal after injury and G protein-coupled receptors are involved in the vascular smooth muscle cell (VSMC) proliferation required to form intimal hyperplasia. We have previously identified the role of Gαq in VSMC proliferation in vitro. This study now examines the role of Gαq in the developing intimal hyperplasia in a murine model and the impact of disruption of Gαq signaling on intimal hyperplasia development. Methods The murine femoral wire injury model was employed in which a micro wire is passed through a branch of the femoral artery and used to denude the common femoral artery. Specimens were perfusion-fixed and sections were stained with H&E and Movat’s stains such that morphometric analysis could be performed using an Image-Pro system. Additional specimens of femoral artery were also harvested and snap frozen for western blotting or zymography to allow for the study of G protein expression and both protease expression and activity. Contralateral vessels were used as controls. Additional vessels were immersed in pluronic gel containing the chemical Gαq G protein inhibitors GP-2A, siRNA to Gαq or advenovirus containing mutant inactive Gαq. Results Gαq expression increased in a time-dependent manner after femoral artery injury. Sham operated on vessels did not produce such a response. Inhibition of Gαq reduced cell proliferation without affecting cell migration. Interruption of Gαq signaling also inhibited the development of intimal hyperplasia. Inhibition of Gαq did not alter peak uPA activity and expression but did increase early PAI-1 activity and expression. Inhibition of Gαq reduced peak MMP-9 activity at day 3 but did not influence peak MMP-2 activity at day 7. Protein expression for MMP-9 was also decreased but that of MMP-2 was not affected. There were no changes in the expression or the activity of the respective inhibitors for MMP-9 and MMP-2, TIMP-1 and TIMP-2. Conclusions These data demonstrate that femoral wire injury in the mouse is associated with a time-dependent increase in Gαq expression. Inhibition of Gαq alters cell proliferation and is associated with decreased MMP-9 expression and activity.

show abstract

Characterization of the angiotensin II AT₁ receptor subtype involved in DNA synthesis in cultured vascular smooth muscle cells

Cited by 14 publications

References 44 publications

Angiotensin AT1 receptor antagonism and protection against cardiovascular end-organ damage

Angiotensin AT1 receptor antagonism and protection against cardiovascular end-organ damage

Transactivation of the Epidermal Growth Factor Receptor by Angiotensin II in Glomerular Podocytes

Gαq G proteins modulate MMP-9 gelatinase during remodeling of the murine femoral artery

Contact Info

Product

Resources

About

Characterization of the angiotensin II AT1 receptor subtype involved in DNA synthesis in cultured vascular smooth muscle cells

Cited by 14 publications

References 44 publications

Angiotensin AT1 receptor antagonism and protection against cardiovascular end-organ damage

Angiotensin AT1 receptor antagonism and protection against cardiovascular end-organ damage

Transactivation of the Epidermal Growth Factor Receptor by Angiotensin II in Glomerular Podocytes

Gαq G proteins modulate MMP-9 gelatinase during remodeling of the murine femoral artery

Contact Info

Product

Resources

About

Characterization of the angiotensin II AT₁ receptor subtype involved in DNA synthesis in cultured vascular smooth muscle cells