Angiotensin II Type 1 Receptor Blockade Inhibits the Expression of Immediate-Early Genes and Fibronectin in Rat Injured Artery

Kim, Shokei; Kawamura, Masaki; Wanibuchi, Hideki; Ohta, Kensuke; Hamaguchi, Akinori; Omura, Takashi; Yukimura, Tokihito; Miura, Katsuyuki; Itoh, Hiroshi

doi:10.1161/01.cir.92.1.88

Cited by 101 publications

(68 citation statements)

References 46 publications

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“…However, it is dramatically induced following balloon dilatation of the carotid artery [8] or on denudation of arterial endothelium [7,42]. In injured vascular cells, Egr-1 is rapidly activated and found to be involved in profound chemotactic and mitogenic effects, which may contribute to the structural remodeling that typically occurs in the pathogenesis of vascular diseases [7,43].…”

Section: Discussionmentioning

confidence: 99%

“…Early growth response factor 1 (Egr-1), an 80-82-kDa zinc finger transcription factor, has a low basal level in the normal vessel wall, but has been shown to rapidly and transiently express in SMCs and endothelial cells in response to arterial injury [7,8]. Once activated, Egr-1 regulates the expression of several genes, including monocyte chemotactic protein-1 (MCP-1), platelet-derived growth factor (PDGF) A and B [7,9,10], and Cyclin D1 [11,12].…”

Section: Introductionmentioning

confidence: 99%

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Berberine suppresses MEK/ERK-dependent Egr-1 signaling pathway and inhibits vascular smooth muscle cell regrowth after in vitro mechanical injury

Liang

Ting

Yin

et al. 2006

Biochemical Pharmacology

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Vascular smooth muscle cell (SMC) proliferation plays an important role in the pathogenesis of atherosclerosis and post-angioplasty restenosis. Berberine is a well-known component of the Chinese herb medicine Huanglian (Coptis chinensis), and is capable of inhibiting SMC contraction and proliferation, yet the exact mechanism is unknown. We therefore investigated the effect of berberine on SMC growth after mechanic injury in vitro. DNA synthesis and cell proliferation assay were performed to show that berberine inhibited serum-stimulated rat aortic SMC growth in a concentration-dependent manner. Mechanical injury with sterile pipette tip stimulated the regrowth of SMCs. Treatment with berberine prevented the regrowth and migration of SMCs into the denuded trauma zone. Western blot analysis showed that activation of the MEK1/2 (mitogen-activated protein kinase kinase 1/2), extracellular signal-regulated kinase (ERK), and up-regulation of early growth response gene (Egr-1), c-Fos and Cyclin D1 were observed sequentially after mechanic injury in vitro. Semi-quantitative reverse-transcription PCR assay further confirmed the increase of Egr-1, cFos, platelet-derived growth factor (PDGF) and Cyclin D1 expression in a transcriptional level. However, berberine significantly attenuated MEK/ERK activation and downstream target (Egr-1, cFos, Cyclin D1 and PDGF-A) expression after mechanic injury in vitro. Our study showed that berberine blocked injury-induced SMC regrowth by inactivation of ERK/Egr-1 signaling pathway thereby preventing early signaling induced by injury in vitro. The anti-proliferative properties of berberine may be useful in treating disorders due to inappropriate SMC growth.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Berberine suppresses MEK/ERK-dependent Egr-1 signaling pathway and inhibits vascular smooth muscle cell regrowth after in vitro mechanical injury

Liang

Ting

Yin

et al. 2006

Biochemical Pharmacology

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“…10,15 Interestingly, recent studies indicate that Egr-1 is expressed by SMCs as they migrate from the media toward the intima after injury. 16 Egr-1 binds to the proximal promoters of many genes implicated in the proliferative and chemotactic response to injury.…”

Section: Discussionmentioning

confidence: 99%

“…14 In the normal rat vessel wall, Egr-1 is expressed at low or undetectable levels. However, it is dramatically induced following balloon dilatation of the carotid artery 15 or on denudation of arterial endothelium. 10,16 Since Egr-1 positively regulates the expression of multiple genes implicated in the proliferative response to injury, targeting this transcription factor in SMCs may ultimately be useful in efforts to reduce the incidence of restenosis after angioplasty.…”

mentioning

confidence: 99%

Vascular Smooth Muscle Cell Proliferation and Regrowth after Mechanical Injury in Vitro Are. Egr-1/NGFI-A-Dependent

Santiago

Atkins

Khachigian

1999

The American Journal of Pathology

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Smooth muscle cell (SMC) proliferation is a key event in renarrowing of blood vessels after balloon angioplasty. Mechanical injury imparted to the arterial wall in experimental models induces the expression of the immediate-early gene , egr-1. Egr-1 binds to and activates expression from the proximal promoters of multiple genes whose products can , in turn , influence the vascular response to injury. Here , we used antisense strategies in vitro to inhibit rat vascular SMC proliferation by directly targeting Egr-1. A series of phosphorothioate antisense oligonucleotides of 15 base length and complementary to various theoretically accessible regions within Egr-1 mRNA were synthesized and assessed for their ability to selectively inhibit SMC proliferation in an Egr-1-dependent manner. Western blot analysis revealed that two oligonucleotides , AS2 and E11 , inhibited Egr-1 synthesis in cells exposed to serum without affecting levels of the zinc finger protein Sp1. AS2 and E11 inhibited seruminducible [ 3 H]thymidine incorporation into DNA, as well as serum stimulation of total cell numbers. Sizematched phosphorothioate oligonucleotides with random , scrambled , sense or mismatch sequences failed to inhibit. Antisense Egr-1 inhibition was nontoxic and reversible. These oligonucleotides also inhibited SMC regrowth after mechanical injury in vitro. Egr-1 thus plays a key regulatory role in SMC proliferation and repair following injury. (Am J Pathol 1999, 155:897-905)

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“…At 2 days after gene transfer, the endothelial denudation of the left common carotid artery was carried out by three passages of a Fogarty 2F balloon catheter (Baxter Healthcare, Deerfield, IL, USA) through the left femoral artery, as previously described. 12,28 Measurement of ratio of intimal/medial areas For the estimation of ratio of intimal/medial areas (I/M ratio), at 14 days after balloon injury, rats were anesthetized with ether, and carotid arteries were fixed by perfusion of 10% (wt/vol) formaldehyde for 15 min under constant pressure, removed, embedded in paraffin and sectioned at 3 m thickness. Cross-sections were stained with Elastica Van Gieson, and hematoxylin and eosin.…”

Section: In Vivo Gene Transfer Of Dn-c-jun and Balloon Injurymentioning

confidence: 99%

Dominant negative c-Jun gene transfer inhibits vascular smooth muscle cell proliferation and neointimal hyperplasia in rats

et al. 2001

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Angiotensin II Type 1 Receptor Blockade Inhibits the Expression of Immediate-Early Genes and Fibronectin in Rat Injured Artery

Cited by 101 publications

References 46 publications

Berberine suppresses MEK/ERK-dependent Egr-1 signaling pathway and inhibits vascular smooth muscle cell regrowth after in vitro mechanical injury

Berberine suppresses MEK/ERK-dependent Egr-1 signaling pathway and inhibits vascular smooth muscle cell regrowth after in vitro mechanical injury

Vascular Smooth Muscle Cell Proliferation and Regrowth after Mechanical Injury in Vitro Are. Egr-1/NGFI-A-Dependent

Dominant negative c-Jun gene transfer inhibits vascular smooth muscle cell proliferation and neointimal hyperplasia in rats

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